<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01684878</url>
  </required_header>
  <id_info>
    <org_study_id>MO28113</org_study_id>
    <secondary_id>2011-005975-17</secondary_id>
    <nct_id>NCT01684878</nct_id>
  </id_info>
  <brief_title>Pertuzumab in Platinum-Resistant Low Human Epidermal Growth Factor Receptor 3 (HER3) Messenger Ribonucleic Acid (mRNA) Epithelial Ovarian Cancer (PENELOPE)</brief_title>
  <official_title>A Two-Part, Randomized Phase III, Double-Blind, Multicenter Trial Assessing The Efficacy And Safety of Pertuzumab In Combination With Standard Chemotherapy Vs. Placebo Plus Standard Chemotherapy In Women With Recurrent Platinum-Resistant Epithelial Ovarian Cancer And Low HER3 mRNA Expression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <brief_summary>
    <textblock>
      This two-part, multicenter study will evaluate the safety, tolerability and efficacy of&#xD;
      pertuzumab in combination with standard chemotherapy in women with recurrent&#xD;
      platinum-resistant epithelial ovarian cancer. In the non-randomized Part 1 safety run-in,&#xD;
      participants will receive pertuzumab plus either topotecan or paclitaxel. In the randomized,&#xD;
      double-blind Part 2 of the study, participants will receive either pertuzumab or placebo in&#xD;
      combination with chemotherapy (topotecan, paclitaxel, or gemcitabine).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 22, 2012</start_date>
  <completion_date type="Actual">April 28, 2016</completion_date>
  <primary_completion_date type="Actual">January 30, 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1: Percentage of Participants With Adverse Events (AEs)</measure>
    <time_frame>Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)</time_frame>
    <description>An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO)</measure>
    <time_frame>Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)</time_frame>
    <description>PFS (IRC-Assessed) was defined as the time from randomization into Part 2 of the trial until progressive disease (PD), MBO or death from any cause, whichever occurred first per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1- Objective Response Rate (ORR)</measure>
    <time_frame>Approximately 28 months (assessed at baseline and every 9 weeks from randomization until disease progression)</time_frame>
    <description>ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (&lt;)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2- Objective Response Rate (ORR)</measure>
    <time_frame>Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)</time_frame>
    <description>ORR was defined as the number of participants with BOR of CR or PR recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (&lt;)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: PFS Assessed by the Investigator</measure>
    <time_frame>Approximately 28 months (assessed at screening and every 9 weeks from randomization until disease progression)</time_frame>
    <description>PFS as assessed by Investigator was defined as the time from first dose of pertuzumab or chemotherapy in Part 1 of the trial, until disease progression according to RECIST version 1.1, symptomatic deterioration or death from any cause, whichever occurs first. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants were censored at the last tumor assessment. Participants who have no tumor assessments after baseline and who were still alive will be censored at 1 day.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Progression-free Survival (PFS) Assessed by the Investigator</measure>
    <time_frame>Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)</time_frame>
    <description>PFS (Investigator-assessed) is defined as the time from randomization, until disease progression according to RECIST v1.1 including death or MBO, whichever occurs first. Censoring is based on the last tumor assessment. If no tumor assessment post baseline, then censoring is at day 1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score</measure>
    <time_frame>Baseline (assessed at baseline and every 9 weeks from randomization until disease progression)</time_frame>
    <description>EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scores, a higher score represents a more severe level of symptoms. For the global health status scores, a higher score represents a better quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Percentage of Participants With Adverse Events (AEs)</measure>
    <time_frame>Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)</time_frame>
    <description>An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Overall Survival</measure>
    <time_frame>Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)</time_frame>
    <description>Overall survival was defined as the time from randomization into Part 2 of the trial until death from any cause</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">208</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>Part 1: Pertuzumab + Topotecan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Pertuzumab + Paclitaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Pertuzumab+Chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Placebo+Chemotherapy</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine (Chemotherapy)</intervention_name>
    <description>Participants administered gemcitabine at a dosage of 1000 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Days 1 and 8 every 3 weeks.</description>
    <arm_group_label>Part 2: Pertuzumab+Chemotherapy</arm_group_label>
    <arm_group_label>Part 2: Placebo+Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel (Chemotherapy)</intervention_name>
    <description>Participants administered paclitaxel at a dosage of 80 mg/m^2 as 1 hour IV infusion on Days 1, 8 and 15 every 3 weeks.</description>
    <arm_group_label>Part 1: Pertuzumab + Paclitaxel</arm_group_label>
    <arm_group_label>Part 1: Pertuzumab + Topotecan</arm_group_label>
    <arm_group_label>Part 2: Pertuzumab+Chemotherapy</arm_group_label>
    <arm_group_label>Part 2: Placebo+Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pertuzumab</intervention_name>
    <description>Participants administered pertuzumab 840 milligrams (mg) IV infusion on Day 1 of the first treatment cycle as a loading dose, followed by 420 mg on Day 1 of each subsequent 3 weekly cycle.</description>
    <arm_group_label>Part 1: Pertuzumab + Paclitaxel</arm_group_label>
    <arm_group_label>Part 1: Pertuzumab + Topotecan</arm_group_label>
    <arm_group_label>Part 2: Pertuzumab+Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants administered pertuzumab matching placebo IV infusion on Day 1 of each 3 weekly cycle.</description>
    <arm_group_label>Part 1: Pertuzumab + Paclitaxel</arm_group_label>
    <arm_group_label>Part 2: Placebo+Chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topotecan (Chemotherapy)</intervention_name>
    <description>Participants administered topotecan at a dosage of 1.25 mg/m^2 as a 30 minute IV infusion daily on Days 1 to 5 every 3 weeks.</description>
    <arm_group_label>Part 1: Pertuzumab + Topotecan</arm_group_label>
    <arm_group_label>Part 2: Pertuzumab+Chemotherapy</arm_group_label>
    <arm_group_label>Part 2: Placebo+Chemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed epithelial ovarian, primary peritoneal,&#xD;
             and/or fallopian tube cancer that is platinum-resistant or refractory&#xD;
&#xD;
          -  Low Human epidermal growth factor receptor (HER) 3 messenger ribonucleic acid (mRNA)&#xD;
             expression&#xD;
&#xD;
          -  At least one measurable and/or non-measurable lesion according to Response Evaluation&#xD;
             Criteria in Solid Tumors (RECIST) version (V) 1.1&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) greater than or equal to (&gt;/=) 50 percent&#xD;
             (%)&#xD;
&#xD;
          -  Negative serum pregnancy test in women of childbearing potential&#xD;
&#xD;
          -  Women of childbearing potential must agree to use effective contraception as defined&#xD;
             by protocol during and for at least 6 months post study treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-epithelial tumors&#xD;
&#xD;
          -  Ovarian tumors with low malignant potential (borderline tumors)&#xD;
&#xD;
          -  History of other malignancy of prognostic relevance within the last 5 years, except&#xD;
             for carcinoma in situ of the cervix or basal cell carcinoma, or tumors with a&#xD;
             negligible risk for metastasis or death, such as adequately controlled basal-cell&#xD;
             carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or&#xD;
             carcinoma in situ of the breast&#xD;
&#xD;
          -  Previous treatment with more than 2 chemotherapy regimens&#xD;
&#xD;
          -  Any prior radiotherapy to the pelvis or abdomen&#xD;
&#xD;
          -  History or evidence on physical/neurological examination of central nervous system&#xD;
             disease unrelated to cancer (uncontrolled seizures), unless adequately treated with&#xD;
             standard medical therapy&#xD;
&#xD;
          -  Pre-existing peripheral neuropathy &gt;/= common toxicity criteria (CTC) grade 2&#xD;
             (applicable for paclitaxel cohort only)&#xD;
&#xD;
          -  Inadequate organ function&#xD;
&#xD;
          -  Uncontrolled hypertension or clinically significant cardiovascular disease&#xD;
&#xD;
          -  Current known infection with human immunodeficiency virus (HIV) or active infection&#xD;
             with hepatitis B virus (HBV), or hepatitis C virus (HCV)&#xD;
&#xD;
          -  Current chronic daily treatment with corticosteroids (&gt;/= 10 mg per day of&#xD;
             methylprednisolone or equivalent), excluding inhaled steroids&#xD;
&#xD;
          -  History of receiving any investigational treatment within 28 days prior to first study&#xD;
             drug administration&#xD;
&#xD;
          -  For Part 2 of the trial: prior enrollment into Part 1 of the trial&#xD;
&#xD;
          -  Concurrent participation in any therapeutic clinical trial&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie</name>
      <address>
        <city>Innsbruck</city>
        <zip>6020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie</name>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven Gasthuisberg</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Herlev Hospital; Onkologisk afdeling</name>
      <address>
        <city>Herlev</city>
        <zip>2730</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet, Onkologisk Klinik</name>
      <address>
        <city>København Ø</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Bergonie; Oncologie</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Francois Baclesse; Oncologie</name>
      <address>
        <city>Caen</city>
        <zip>14076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Georges Francois Leclerc; Oncologie 3</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CRLCC Val dAurelle Paul Lam</name>
      <address>
        <city>Montpellier cedex 5</city>
        <zip>34298</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Tenon; Oncologie Radiotherapie</name>
      <address>
        <city>Paris</city>
        <zip>75970</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ch Lyon Sud; Chir Onc Gyne Sct Jules Courmont</name>
      <address>
        <city>Pierre Benite</city>
        <zip>69310</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinique Armoricaine Radiologie; Hopital de Jour</name>
      <address>
        <city>Plerin</city>
        <zip>22190</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ico Rene Gauducheau; Oncologie</name>
      <address>
        <city>Saint Herblain</city>
        <zip>44805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Alexis Vautrin; Oncologie Medicale</name>
      <address>
        <city>Vandoeuvre Les Nancy</city>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy; Oncologie Medicale</name>
      <address>
        <city>Villejuif</city>
        <zip>94800</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum &quot;Carl Gustav Carus&quot;; Frauenheilkunde und Geburtshilfe</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Evangelischen Krankenhauses Düsseldorf; Frauenklinik</name>
      <address>
        <city>Düsseldorf</city>
        <zip>40217</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Essen; Zentrum Für Frauenheilkunde</name>
      <address>
        <city>Essen</city>
        <zip>45122</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kliniken Essen-Mitte Evang. Huyssens-Stiftung, Klinik für Gynäkologie und gynäkologische Onkologie</name>
      <address>
        <city>Essen</city>
        <zip>45136</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Freiburg; Frauenklinik</name>
      <address>
        <city>Freiburg</city>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Greifswald; Klinik für Frauenheilkunde und Brustzentrum</name>
      <address>
        <city>Greifswald</city>
        <zip>17475</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Hamburg-Eppendorf (UKE); Klinik und Poliklinik für Gynäkologie</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding</name>
      <address>
        <city>Hannover</city>
        <zip>30177</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNI-Klinikum Campus Kiel Klinik f.Gynäkologie u.Geburtshilfe</name>
      <address>
        <city>Kiel</city>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe</name>
      <address>
        <city>Koeln</city>
        <zip>50935</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Konstanz, Frauenklinik</name>
      <address>
        <city>Konstanz</city>
        <zip>78464</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum rechts der Isar der TU München; Frauenklinik &amp; Poliklinik</name>
      <address>
        <city>München</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie &amp; Geburtshilfe</name>
      <address>
        <city>Offenbach</city>
        <zip>63069</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hämatologisch/Onkologische Praxis Dr. Herbrick - Zipp/Prof. Dr. Decker, Studienzentrum</name>
      <address>
        <city>Ravensburg</city>
        <zip>88212</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsfrauen- und Poliklinik am Klinikum Suedstadt</name>
      <address>
        <city>Rostock</city>
        <zip>18059</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinik Tübingen; Frauenklinik</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Ulm Am Michelsberg; Frauenklinik</name>
      <address>
        <city>Ulm</city>
        <zip>89075</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HELIOS Dr. Horst Schmidt Kliniken Wiesbaden; Klinik für Gynäkologie und gynäkologische Onkologie</name>
      <address>
        <city>Wiesbaden</city>
        <zip>65199</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Tumori Napoli;Unità Operativa Oncologia Medica Uro-Ginecologica</name>
      <address>
        <city>Napoli</city>
        <state>Campania</state>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Regina Elena; Oncologia Medica A</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ente Ospedaliero Ospedali Galliera; S.C. Oncologia Medica</name>
      <address>
        <city>Genova</city>
        <state>Liguria</state>
        <zip>16128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.Spedali Civili; Ostetricia e Ginecologia</name>
      <address>
        <city>Brescia</city>
        <state>Lombardia</state>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo Di Oncologia</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U Pisana; Dipartimento di Ginecologia Oncologica</name>
      <address>
        <city>Pisa</city>
        <state>Toscana</state>
        <zip>56126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antoni van Leeuwenhoek Ziekenhuis</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academ Ziekenhuis Groningen; Medical Oncology</name>
      <address>
        <city>Groningen</city>
        <zip>9713 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academisch Ziekenhuis Leiden; Clinical Oncology</name>
      <address>
        <city>Leiden</city>
        <zip>2333 ZA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMC St Radboud</name>
      <address>
        <city>Nijmegen</city>
        <zip>6525 GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Norvegian Radium Hospital Montebello; Dept of Oncology</name>
      <address>
        <city>Oslo</city>
        <zip>0379</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Corporacio Sanitaria Parc Tauli; Servicio de Oncologia</name>
      <address>
        <city>Sabadell</city>
        <state>Barcelona</state>
        <zip>08208</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Son Llatzer; Servicio de Oncologia</name>
      <address>
        <city>Palma de Mallorca</city>
        <state>Islas Baleares</state>
        <zip>07198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Univ Vall d'Hebron; Servicio de Oncologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic i Provincial; Servicio de Hematología y Oncología</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Duran i Reynals; Oncologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Reina Sofia; Servicio de Oncologia</name>
      <address>
        <city>Cordoba</city>
        <zip>14004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia</name>
      <address>
        <city>Girona</city>
        <zip>17007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia</name>
      <address>
        <city>Lerida</city>
        <zip>25198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañon; Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Oncologico MD Anderson Internacional; Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <zip>28033</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre; Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz; Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Regional Universitario Carlos Haya; Servicio de Oncologia</name>
      <address>
        <city>Malaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia</name>
      <address>
        <city>Murcia</city>
        <zip>30120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Valenciano Oncologia; Oncologia Medica</name>
      <address>
        <city>Valencia</city>
        <zip>46009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario la Fe; Servicio de Oncologia</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Miguel Servet; Servicio Oncologia</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitetssjukhuset; Onkologkliniken</name>
      <address>
        <city>Linkoeping</city>
        <zip>58185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skånes University Hospital, Skånes Department of Onclology</name>
      <address>
        <city>Lund</city>
        <zip>22185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Norway</country>
    <country>Spain</country>
    <country>Sweden</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <results_first_submitted>October 3, 2016</results_first_submitted>
  <results_first_submitted_qc>October 3, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">November 23, 2016</results_first_posted>
  <last_update_submitted>April 13, 2017</last_update_submitted>
  <last_update_submitted_qc>April 13, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Topotecan</mesh_term>
    <mesh_term>Pertuzumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 208 participants were entered into the study, 52 participants in Part 1, and 156 participants in Part 2 of the study. Of these, 203 received treatment with pertuzumab or pertuzumab-placebo (50 participants in Part 1 and 153 participants in Part 2).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part 1: Pertuzumab + Topotecan</title>
          <description>Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
        </group>
        <group group_id="P2">
          <title>Part 1: Pertuzumab + Paclitaxel</title>
          <description>Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
        </group>
        <group group_id="P3">
          <title>Part 2: Pertuzumab+Chemotherapy</title>
          <description>Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
        </group>
        <group group_id="P4">
          <title>Part 2: Placebo+Chemotherapy</title>
          <description>Participants received pertuzumab-matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part 1: Safety Run in Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="28"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="23"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Participants withdrawn consent</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part 2: Randomized Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="78"/>
                <participants group_id="P4" count="78"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Participants Randomized But Not Treated</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Participants Mis-randomized</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="78"/>
                <participants group_id="P4" count="78"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Participant withdrew consent</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="62"/>
                <participants group_id="P4" count="68"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Alive at data-cut</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="13"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant noncompliance</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Part 1: all participants enrolled and treated in Part 1 of the study ('as treated' analysis) and Part 2: intent-to-treat (ITT) population was defined as all randomized participants in the group to which they were randomly assigned ('as randomized' analysis).</population>
      <group_list>
        <group group_id="B1">
          <title>Part 1: Pertuzumab + Topotecan</title>
          <description>Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
        </group>
        <group group_id="B2">
          <title>Part 1: Pertuzumab + Paclitaxel</title>
          <description>Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
        </group>
        <group group_id="B3">
          <title>Part 2: Pertuzumab+Chemotherapy</title>
          <description>Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
        </group>
        <group group_id="B4">
          <title>Part 2: Placebo+Chemotherapy</title>
          <description>Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="22"/>
            <count group_id="B2" value="28"/>
            <count group_id="B3" value="78"/>
            <count group_id="B4" value="78"/>
            <count group_id="B5" value="206"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Less than or equal to (≤)65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="40"/>
                    <measurement group_id="B4" value="44"/>
                    <measurement group_id="B5" value="116"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Greater than (&gt;)65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="38"/>
                    <measurement group_id="B4" value="34"/>
                    <measurement group_id="B5" value="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="78"/>
                    <measurement group_id="B4" value="78"/>
                    <measurement group_id="B5" value="206"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Part 1: Percentage of Participants With Adverse Events (AEs)</title>
        <description>An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
        <time_frame>Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)</time_frame>
        <population>All Treated population included all participants enrolled and treated in Part 1 of the study ('as treated' analysis) and who had received at least 1 dose of pertuzumab or chemotherapy.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pertuzumab + Topotecan</title>
            <description>Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pertuzumab + Paclitaxel</title>
            <description>Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: Percentage of Participants With Adverse Events (AEs)</title>
          <description>An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
          <population>All Treated population included all participants enrolled and treated in Part 1 of the study ('as treated' analysis) and who had received at least 1 dose of pertuzumab or chemotherapy.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.5"/>
                    <measurement group_id="O2" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO)</title>
        <description>PFS (IRC-Assessed) was defined as the time from randomization into Part 2 of the trial until progressive disease (PD), MBO or death from any cause, whichever occurred first per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.</description>
        <time_frame>Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)</time_frame>
        <population>ITT Population was defined as all randomized participants in the group to which they were randomly assigned ('as randomized' analysis).</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Pertuzumab+Chemotherapy</title>
            <description>Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo+Chemotherapy</title>
            <description>Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO)</title>
          <description>PFS (IRC-Assessed) was defined as the time from randomization into Part 2 of the trial until progressive disease (PD), MBO or death from any cause, whichever occurred first per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.</description>
          <population>ITT Population was defined as all randomized participants in the group to which they were randomly assigned ('as randomized' analysis).</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="78"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.27" lower_limit="3.65" upper_limit="6.11"/>
                    <measurement group_id="O2" value="2.74" lower_limit="2.14" upper_limit="4.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The stratified time-to-event analysis included the treatment group variable plus the following stratification factors: selected chemotherapy cohort (gemcitabine versus topotecan vs paclitaxel), previous anti-angiogenic therapy (yes versus no), and progression-free interval (PFI) since platinum therapy (&lt; 3 months versus 3-6 months). A hazard ratio &lt; 1 favored the pertuzumab + chemotherapy treatment arm.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.4983</p_value>
            <method>2 sided log-rank</method>
            <param_type>Hazard Ratio (stratified)</param_type>
            <param_value>0.88</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.62</ci_lower_limit>
            <ci_upper_limit>1.27</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1- Objective Response Rate (ORR)</title>
        <description>ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (&lt;)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>Approximately 28 months (assessed at baseline and every 9 weeks from randomization until disease progression)</time_frame>
        <population>All Treated participants with measurable disease at baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pertuzumab + Topotecan</title>
            <description>Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pertuzumab + Paclitaxel</title>
            <description>Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1- Objective Response Rate (ORR)</title>
          <description>ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (&lt;)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
          <population>All Treated participants with measurable disease at baseline.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.3"/>
                    <measurement group_id="O2" value="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2- Objective Response Rate (ORR)</title>
        <description>ORR was defined as the number of participants with BOR of CR or PR recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (&lt;)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)</time_frame>
        <population>ITT population with measurable disease at baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Pertuzumab+Chemotherapy</title>
            <description>Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo+Chemotherapy</title>
            <description>Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2- Objective Response Rate (ORR)</title>
          <description>ORR was defined as the number of participants with BOR of CR or PR recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (&lt;)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
          <population>ITT population with measurable disease at baseline.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.8" lower_limit="7.0" upper_limit="26.2"/>
                    <measurement group_id="O2" value="8.7" lower_limit="3.3" upper_limit="18.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.4102</p_value>
            <method>Fisher Exact</method>
            <param_type>Difference in response rate</param_type>
            <param_value>6.06</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>6.0</ci_lower_limit>
            <ci_upper_limit>18.3</ci_upper_limit>
            <estimate_desc>Approximate 95% CI for difference of 2 rates using Hauck-Anderson method.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 1: PFS Assessed by the Investigator</title>
        <description>PFS as assessed by Investigator was defined as the time from first dose of pertuzumab or chemotherapy in Part 1 of the trial, until disease progression according to RECIST version 1.1, symptomatic deterioration or death from any cause, whichever occurs first. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants were censored at the last tumor assessment. Participants who have no tumor assessments after baseline and who were still alive will be censored at 1 day.</description>
        <time_frame>Approximately 28 months (assessed at screening and every 9 weeks from randomization until disease progression)</time_frame>
        <population>All Treated population included all participants enrolled and treated in Part 1 of the study ('as treated' analysis) and who had received at least 1 dose of pertuzumab or chemotherapy.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pertuzumab + Topotecan</title>
            <description>Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pertuzumab + Paclitaxel</title>
            <description>Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 1: PFS Assessed by the Investigator</title>
          <description>PFS as assessed by Investigator was defined as the time from first dose of pertuzumab or chemotherapy in Part 1 of the trial, until disease progression according to RECIST version 1.1, symptomatic deterioration or death from any cause, whichever occurs first. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants were censored at the last tumor assessment. Participants who have no tumor assessments after baseline and who were still alive will be censored at 1 day.</description>
          <population>All Treated population included all participants enrolled and treated in Part 1 of the study ('as treated' analysis) and who had received at least 1 dose of pertuzumab or chemotherapy.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.07" lower_limit="1.94" upper_limit="6.08"/>
                    <measurement group_id="O2" value="4.24" lower_limit="3.45" upper_limit="6.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Progression-free Survival (PFS) Assessed by the Investigator</title>
        <description>PFS (Investigator-assessed) is defined as the time from randomization, until disease progression according to RECIST v1.1 including death or MBO, whichever occurs first. Censoring is based on the last tumor assessment. If no tumor assessment post baseline, then censoring is at day 1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.</description>
        <time_frame>Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)</time_frame>
        <population>ITT Population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis)</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Pertuzumab+Chemotherapy</title>
            <description>Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo+Chemotherapy</title>
            <description>Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Progression-free Survival (PFS) Assessed by the Investigator</title>
          <description>PFS (Investigator-assessed) is defined as the time from randomization, until disease progression according to RECIST v1.1 including death or MBO, whichever occurs first. Censoring is based on the last tumor assessment. If no tumor assessment post baseline, then censoring is at day 1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.</description>
          <population>ITT Population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis)</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="78"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.22" lower_limit="3.25" upper_limit="5.22"/>
                    <measurement group_id="O2" value="3.94" lower_limit="2.63" upper_limit="4.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score</title>
        <description>EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scores, a higher score represents a more severe level of symptoms. For the global health status scores, a higher score represents a better quality of life.</description>
        <time_frame>Baseline (assessed at baseline and every 9 weeks from randomization until disease progression)</time_frame>
        <population>ITT population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis).</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Pertuzumab+Chemotherapy</title>
            <description>Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo+Chemotherapy</title>
            <description>Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score</title>
          <description>EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scores, a higher score represents a more severe level of symptoms. For the global health status scores, a higher score represents a better quality of life.</description>
          <population>ITT population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis).</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="78"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Functional Scales: Physical (n=71, 74)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.1" spread="22.77"/>
                    <measurement group_id="O2" value="74.9" spread="20.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Functional Scales: Role (n=70, 73)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.6" spread="33.16"/>
                    <measurement group_id="O2" value="69.4" spread="32.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Functional Scales: Emotional (n=71, 73)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.5" spread="24.03"/>
                    <measurement group_id="O2" value="65.9" spread="23.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Functional Scales: Cognitive (n=71, 73)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.2" spread="25.34"/>
                    <measurement group_id="O2" value="84.9" spread="20.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Functional Scales: Social (n=71, 73)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.7" spread="30.01"/>
                    <measurement group_id="O2" value="68.3" spread="29.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Symptomatic Scales: Fatigue (n=71, 74)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.2" spread="28.75"/>
                    <measurement group_id="O2" value="38.4" spread="27.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Symptomatic Scales: Nausea and vomiting (n=72, 74)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.4" spread="15.68"/>
                    <measurement group_id="O2" value="12.4" spread="20.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Symptomatic Scales: Pain (n=72, 74)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.2" spread="31.34"/>
                    <measurement group_id="O2" value="31.1" spread="29.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Symptomatic Scales: Dyspnoea (n=68, 73)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.5" spread="28.47"/>
                    <measurement group_id="O2" value="21.5" spread="27.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Symptomatic Scales: Insomnia (n=69, 74)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.3" spread="31.25"/>
                    <measurement group_id="O2" value="31.5" spread="31.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Symptomatic Scales: Appetite loss (n=71, 73)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.9" spread="30.19"/>
                    <measurement group_id="O2" value="21.0" spread="26.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Symptomatic Scales: Constipation (n=69, 72)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.6" spread="32.41"/>
                    <measurement group_id="O2" value="26.4" spread="32.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Symptomatic Scales: Diarrhoea (n=69, 72)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.5" spread="26.49"/>
                    <measurement group_id="O2" value="14.4" spread="22.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Symptomatic Scales:Financial difficulties(n=70,72</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.6" spread="28.78"/>
                    <measurement group_id="O2" value="13.4" spread="22.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Global health status / QoL scale (n=71, 72)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.1" spread="24.99"/>
                    <measurement group_id="O2" value="61.1" spread="22.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Percentage of Participants With Adverse Events (AEs)</title>
        <description>An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
        <time_frame>Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)</time_frame>
        <population>Safety population included all participants who had received at least 1 dose of pertuzumab, pertuzumab-placebo, or chemotherapy.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Pertuzumab+Chemotherapy</title>
            <description>Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo+Chemotherapy</title>
            <description>Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Percentage of Participants With Adverse Events (AEs)</title>
          <description>An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
          <population>Safety population included all participants who had received at least 1 dose of pertuzumab, pertuzumab-placebo, or chemotherapy.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="77"/>
                <count group_id="O2" value="76"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.7"/>
                    <measurement group_id="O2" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Overall Survival</title>
        <description>Overall survival was defined as the time from randomization into Part 2 of the trial until death from any cause</description>
        <time_frame>Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)</time_frame>
        <population>ITT Population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis)</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Pertuzumab+Chemotherapy</title>
            <description>Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo+Chemotherapy</title>
            <description>Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Overall Survival</title>
          <description>Overall survival was defined as the time from randomization into Part 2 of the trial until death from any cause</description>
          <population>ITT Population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis)</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="78"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.18" lower_limit="6.67" upper_limit="15.24"/>
                    <measurement group_id="O2" value="8.36" lower_limit="6.14" upper_limit="11.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The stratified time-to-event analysis included the treatment group variable plus the following stratification factors: selected chemotherapy cohort (gemcitabine versus topotecan versus paclitaxel), previous angiogenic therapy (yes versus no) and PFI since platinum therapy (&lt;3 months versus 3-6 months).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.5960</p_value>
            <method>2 sided log-rank</method>
            <param_type>Hazard ratio (stratified)</param_type>
            <param_value>0.90</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.61</ci_lower_limit>
            <ci_upper_limit>1.32</ci_upper_limit>
            <estimate_desc>A hazard ratio &lt; 1 favored the Pertuzumab + Chemotherapy treatment group</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Part 1: Pertuzumab + Topotecan</title>
          <description>Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
        </group>
        <group group_id="E2">
          <title>Part 1: Pertuzumab + Paclitaxel</title>
          <description>Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.</description>
        </group>
        <group group_id="E3">
          <title>Part 2: Pertuzumab+Chemotherapy</title>
          <description>Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
        </group>
        <group group_id="E4">
          <title>Part 2: Placebo+Chemotherapy</title>
          <description>Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="29" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="33" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Bone Marrow Failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Coronary Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Acute Myocardial Infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Angina Pectoris</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Cardiac Failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Intestinal Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Subileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Lower</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Anal Fissure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Duodenal Fistula</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>General Physical Health Deterioration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Performance Status Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Not yet coded</sub_title>
                <description>This adverse event was not coded at the time of the primary analysis. The preferred term will be reported when available at the final analysis.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abdominal Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Device Related Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Peritonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Anal Abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Encephalitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Infective Myositis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Kidney Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Meningitis Pneumococcal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Staphylococcal Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contrast Media Reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Femoral Neck Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Humerus Fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Platelet Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Weight Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Ovarian Cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral Ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Hydrocephalus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Ischaemic Stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Urinary Tract Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Urinary Tract Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal Fistula</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Eczema Asteatotic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep Vein Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (17.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="72" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="75" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="28" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="32" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="23" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="21" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Thrombocytosis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="50" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="23" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="31" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="34" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="23" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="21" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="22" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Upper</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Rectal Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal Reflux Disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="32" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="24" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="24" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="12" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Mucosal Inflammation</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Oedema Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Influenza Like Illness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Nail Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight Decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Ejection Fraction Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Lymphocyte Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>White Blood Cell Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Gamma-Glutamyltransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Neutrophil Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Blood Alkaline Phosphatase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Platelet Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Blood Creatinine Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="17" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Muscle Spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral Sensory Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Neuropathy Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Ageusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Peripheral Motor Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="12" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="21" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Palmar-Plantar Erythrodysaesthesia Syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Nail Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pain Of Skin</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Rash Maculo-Papular</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-La Roche</organization>
      <phone>800 821-8590</phone>
      <email>genentech@druginfo.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01684878
org study id: MO28113
secondary id: 2011-005975-17
nct id: NCT01684878
lead sponsor: 
This two-part, multicenter study will evaluate the safety, tolerability and efficacy of
      pertuzumab in combination with standard chemotherapy in women with recurrent
      platinum-resistant epithelial ovarian cancer. In the non-randomized Part 1 safety run-in,
      participants will receive pertuzumab plus either topotecan or paclitaxel. In the randomized,
      double-blind Part 2 of the study, participants will receive either pertuzumab or placebo in
      combination with chemotherapy (topotecan, paclitaxel, or gemcitabine).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Part 1: Percentage of Participants With Adverse Events (AEs)
time frame: Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)
description: An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
measure: Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO)
time frame: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
description: PFS (IRC-Assessed) was defined as the time from randomization into Part 2 of the trial until progressive disease (PD), MBO or death from any cause, whichever occurred first per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
measure: Part 1- Objective Response Rate (ORR)
time frame: Approximately 28 months (assessed at baseline and every 9 weeks from randomization until disease progression)
description: ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
measure: Part 2- Objective Response Rate (ORR)
time frame: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
description: ORR was defined as the number of participants with BOR of CR or PR recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
measure: Part 1: PFS Assessed by the Investigator
time frame: Approximately 28 months (assessed at screening and every 9 weeks from randomization until disease progression)
description: PFS as assessed by Investigator was defined as the time from first dose of pertuzumab or chemotherapy in Part 1 of the trial, until disease progression according to RECIST version 1.1, symptomatic deterioration or death from any cause, whichever occurs first. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants were censored at the last tumor assessment. Participants who have no tumor assessments after baseline and who were still alive will be censored at 1 day.
measure: Part 2: Progression-free Survival (PFS) Assessed by the Investigator
time frame: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
description: PFS (Investigator-assessed) is defined as the time from randomization, until disease progression according to RECIST v1.1 including death or MBO, whichever occurs first. Censoring is based on the last tumor assessment. If no tumor assessment post baseline, then censoring is at day 1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
measure: Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score
time frame: Baseline (assessed at baseline and every 9 weeks from randomization until disease progression)
description: EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scores, a higher score represents a more severe level of symptoms. For the global health status scores, a higher score represents a better quality of life.
measure: Part 2: Percentage of Participants With Adverse Events (AEs)
time frame: Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)
description: An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
measure: Part 2: Overall Survival
time frame: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
description: Overall survival was defined as the time from randomization into Part 2 of the trial until death from any cause
arm group label: Part 1: Pertuzumab + Topotecan
arm group type: Experimental
description: Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.
arm group label: Part 1: Pertuzumab + Paclitaxel
arm group type: Experimental
description: Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.
arm group label: Part 2: Pertuzumab+Chemotherapy
arm group type: Experimental
description: Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
arm group label: Part 2: Placebo+Chemotherapy
arm group type: Placebo Comparator
description: Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.
intervention type: Drug
intervention name: Gemcitabine (Chemotherapy)
description: Participants administered gemcitabine at a dosage of 1000 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Days 1 and 8 every 3 weeks.
arm group label: Part 2: Pertuzumab+Chemotherapy
arm group label: Part 2: Placebo+Chemotherapy
intervention type: Drug
intervention name: Paclitaxel (Chemotherapy)
description: Participants administered paclitaxel at a dosage of 80 mg/m^2 as 1 hour IV infusion on Days 1, 8 and 15 every 3 weeks.
arm group label: Part 1: Pertuzumab + Paclitaxel
arm group label: Part 1: Pertuzumab + Topotecan
arm group label: Part 2: Pertuzumab+Chemotherapy
arm group label: Part 2: Placebo+Chemotherapy
intervention type: Drug
intervention name: Pertuzumab
description: Participants administered pertuzumab 840 milligrams (mg) IV infusion on Day 1 of the first treatment cycle as a loading dose, followed by 420 mg on Day 1 of each subsequent 3 weekly cycle.
arm group label: Part 1: Pertuzumab + Paclitaxel
arm group label: Part 1: Pertuzumab + Topotecan
arm group label: Part 2: Pertuzumab+Chemotherapy
intervention type: Drug
intervention name: Placebo
description: Participants administered pertuzumab matching placebo IV infusion on Day 1 of each 3 weekly cycle.
arm group label: Part 1: Pertuzumab + Paclitaxel
arm group label: Part 2: Placebo+Chemotherapy
intervention type: Drug
intervention name: Topotecan (Chemotherapy)
description: Participants administered topotecan at a dosage of 1.25 mg/m^2 as a 30 minute IV infusion daily on Days 1 to 5 every 3 weeks.
arm group label: Part 1: Pertuzumab + Topotecan
arm group label: Part 2: Pertuzumab+Chemotherapy
arm group label: Part 2: Placebo+Chemotherapy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
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country: Austria
country: Belgium
country: Denmark
country: France
country: Germany
country: Italy
country: Netherlands
country: Norway
country: Spain
country: Sweden
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Paclitaxel
mesh term: Gemcitabine
mesh term: Topotecan
mesh term: Pertuzumab
participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 