<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/NCT03783949</url>
  </required_header>
  <id_info>
    <org_study_id>2017-004058-40</org_study_id>
    <nct_id>NCT03783949</nct_id>
  </id_info>
  <brief_title>European Trial on Enhanced DNA Repair Inhibition in Ovarian Cancer</brief_title>
  <acronym>EUDARIO</acronym>
  <official_title>A Multicentre, Open-label, Three-arm Randomised Phase II Trial Assessing the Safety and Efficacy of the HSP90 Inhibitor Ganetespib in Combination With Carboplatin Followed by Maintenance Treatment With Niraparib Versus Ganetespib Plus Carboplatin Followed by Ganetespib and Niraparib Versus Carboplatin in Combination With Standard Chemotherapy Followed by Niraparib Maintenance Treatment in Platinum-sensitive Ovarian Cancer Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>European Commission</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will be performed in women with platinum-sensitive, high-grade serous, high-grade&#xD;
      endometrioid, undifferentiated epithelial ovarian cancer, carcinosarcoma, fallopian tube or&#xD;
      primary peritoneal cancer (proven by central histo-pathological review).&#xD;
&#xD;
      A total of 120 subjects will be randomized (1:1:1) to three different treatment arms: (A)&#xD;
      Standard arm (arm A): Carboplatin (AUC5 d1, q3w i.v.) in combination with Paclitaxel (175&#xD;
      mg/m² d1, q3w i.v.) or Carboplatin (AUC4 d1, q3w i.v.) in combination with Gemcitabine (1000&#xD;
      mg/m² d1, d8, q3w i.v.) followed by maintenance therapy with Niraparib (200/ 300 mg oral&#xD;
      daily, q4w) // (B) First experimental arm (arm B): Ganetespib (150 mg/m2, d1, q3w) in&#xD;
      combination with Carboplatin (AUC5 d1, q3w i.v.) followed by maintenance treatment with&#xD;
      Niraparib (200/ 300 mg oral daily, q4w) // (C) Second experimental arm (arm C): Ganetespib&#xD;
      (150 mg/m² d1, q3w i.v.) plus Carboplatin (AUC5 d1, q3w i.v.) followed by Ganetespib (100&#xD;
      mg/m² d1, d8, d15, d22, q4w i.v.) and Niraparib (200 mg oral daily, q4w).&#xD;
&#xD;
      Chemotherapy treatment will be given for 6 cycles, maintenance treatment with Ganetespib will&#xD;
      be given for a maximum of 9 months or until disease progression, maintenance treatment with&#xD;
      Niraparib can continue until disease progression.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 30, 2018</start_date>
  <completion_date type="Actual">September 1, 2023</completion_date>
  <primary_completion_date type="Actual">September 1, 2023</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Standard arm (arm A): Carboplatin (AUC5 d1, q3w i.v.) in combination with Paclitaxel (175 mg/m² d1, q3w i.v.) or Carboplatin (AUC4 d1, q3w i.v.) in combination with Gemcitabine (1000 mg/m² d1, d8, q3w i.v.) followed by maintenance therapy with Niraparib (200/ 300 mg oral daily, q4w) First experimental arm (arm B): Ganetespib (150 mg/m2, d1, q3w) in combination with Carboplatin (AUC5 d1, q3w i.v.) followed by maintenance treatment with Niraparib (200/ 300 mg oral daily, q4w) Second experimental arm (arm C): Ganetespib (150 mg/m² d1, q3w i.v.) plus Carboplatin (AUC5 d1, q3w i.v.) followed by Ganetespib (100 mg/m² d1, d8, d15, d22, q4w i.v.) and Niraparib (200 mg oral daily, q4w)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Progression-free survival (PFS) by RECIST 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival subgroup analysis</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Progression-free survival subgroup analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-progression PFS (PFS2)</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Post-progression PFS (PFS2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Subsequent Therapy (TFST)</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Time to First Subsequent Therapy (TFST)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Second Subsequent Therapy (TSST)</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Time to Second Subsequent Therapy (TSST)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety: Adverse events (AEs)</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Safety: Adverse events (AEs), measure according to NCI CTCAE, version 4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Objective response rate (ORR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients general health, functionality and well-being assessment using QLQ-C30 questionnaire</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Patient-reported outcome (PRO) questionnaire (QLQ-C30) will be used to assess patient's general health, functionality and well-being</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Overall survival (OS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients general health, functionality and well-being assessment using QLQ-ov28 questionnaire</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Patient-reported outcome (PRO) questionnaire (QLQ-ov28) will be used to assess patient's general health, functionality and well-being</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients gastro-intestinal symptoms using Gastro-intestinal symptoms questionnaire</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Patient-reported outcome (PRO) questionnaire (gastro-intestinal symptoms) will be used to assess patient's gastro-intestinal symptoms</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Biomarker analysis</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Biomarker analysis on DNA level (e.g. free circulating tumour DNA)</description>
  </other_outcome>
  <other_outcome>
    <measure>Biomarker analysis</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Biomarker analysis on RNA level</description>
  </other_outcome>
  <other_outcome>
    <measure>Biomarker analysis</measure>
    <time_frame>3 years 10 months</time_frame>
    <description>Biomarker analysis on protein level (e.g. circulating tumour cells)</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">122</enrollment>
  <condition>Ovarian Cancer</condition>
  <condition>Fallopian Tube Cancer</condition>
  <condition>Primary Peritoneal Carcinoma</condition>
  <arm_group>
    <arm_group_label>Standard arm (arm A)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Carboplatin (AUC5 d1, q3w i.v.) in combination with Paclitaxel (175 mg/m² d1, q3w i.v.) or Carboplatin (AUC4 d1, q3w i.v.) in combination with Gemcitabine (1000 mg/m² d1, d8, q3w i.v.) followed by maintenance therapy with Niraparib (200/ 300 mg oral daily, q4w)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>First experimental arm (arm B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ganetespib (150 mg/m2, d1, q3w) in combination with Carboplatin (AUC5 d1, q3w i.v.) followed by maintenance treatment with Niraparib (200/ 300 mg oral daily, q4w)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Second experimental arm (arm C)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ganetespib (150 mg/m² d1, q3w i.v.) plus Carboplatin (AUC5 d1, q3w i.v.) followed by Ganetespib (100 mg/m² d1, d8, d15, d22, q4w i.v.) and Niraparib (200 mg oral daily, q4w)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ganetespib</intervention_name>
    <description>Ganetespib dose during chemotherapy will be 150mg/m² (q3w) Ganetespib dose during maintenance treatment will be 100mg/m² (q1w)</description>
    <arm_group_label>First experimental arm (arm B)</arm_group_label>
    <arm_group_label>Second experimental arm (arm C)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Niraparib</intervention_name>
    <description>Niraparib starting dose during maintenance treatment will be 200mg or 300mg depending on subject's body weight and subject neutrophil count (QD)</description>
    <arm_group_label>First experimental arm (arm B)</arm_group_label>
    <arm_group_label>Second experimental arm (arm C)</arm_group_label>
    <arm_group_label>Standard arm (arm A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>In combination with Gemcitabine: Carboplatin dose will be AUC4 (q3w) In combination with Paclitaxel: Carboplatin dose will be AUC5 (q3w)</description>
    <arm_group_label>First experimental arm (arm B)</arm_group_label>
    <arm_group_label>Second experimental arm (arm C)</arm_group_label>
    <arm_group_label>Standard arm (arm A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Paclitaxel dose will be 175mg/m² (q3w)</description>
    <arm_group_label>Standard arm (arm A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Gemcitabine dose will be 1000mg/m² (q3w, d1 &amp; d8)</description>
    <arm_group_label>Standard arm (arm A)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must meet the following criteria to be eligible for study entry:&#xD;
&#xD;
               -  Ability to understand and willingness to sign and date a written informed consent&#xD;
                  document&#xD;
&#xD;
               -  Female patients ≥18 years of age&#xD;
&#xD;
               -  High-grade serous, high-grade endometrioid, undifferentiated epithelial ovarian&#xD;
                  cancer, carcinosarcoma, fallopian tube or primary peritoneal cancer&#xD;
&#xD;
               -  Platinum-sensitive relapse &gt;6months after previous platinum-based treatment&#xD;
                  (calculated from the first day of the last cycle of the last platinum-based&#xD;
                  chemotherapy until the date of progression confirmed according to RECIST 1.1 on&#xD;
                  imaging)&#xD;
&#xD;
               -  No limits in number of prior lines&#xD;
&#xD;
               -  Measurable or evaluable disease according to RECIST 1.1&#xD;
&#xD;
               -  ECOG performance status 0-1&#xD;
&#xD;
               -  Adequate functions of the bone marrow&#xD;
&#xD;
          -  Platelets ≥ 100 x 109/L&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L&#xD;
&#xD;
             • Adequate function of the organs&#xD;
&#xD;
          -  Creatinine &lt; 2 mg/dl (&lt;177 μmol/L)&#xD;
&#xD;
          -  Total bilirubin ≤ 1.5 x upper limit of normal (≤ 2.0 in patients with known Gilberts&#xD;
             syndrome) OR direct bilirubin ≤ 1 x ULN&#xD;
&#xD;
          -  SGOT/SGPT (AST/ALT) ≤ 2.5 x upper limit of normal unless liver metastases are present,&#xD;
             in which case they must be ≤ 5 x ULN&#xD;
&#xD;
          -  Urinanalysis or urine dipstick for proteinuria less than 2+. Patients with ≥ 2+ on&#xD;
             dipstick should undergo 24-hour urine collection and must demonstrate &lt; 1 g of&#xD;
             protein/24 hours; except the proteinuria is clearly related to a catheter in the&#xD;
             urinary system.&#xD;
&#xD;
               -  Adequate coagulation parameter: aPTT ≤ 1.5 x ULN (patients on heparin treatment&#xD;
                  must have an aPTT between 1.5-2.5 x ULN), or INR ≤ 1.5. (In patients receiving&#xD;
                  anticoagulants (such as warfarin) INR must be between 2.0 and 3.0 in two&#xD;
                  consecutive measurements 1-4 days apart).&#xD;
&#xD;
               -  Participant receiving corticosteroids (dose &lt; 10 mg/day methylprednisolone&#xD;
                  equivalent), including inhaled steroids, may continue as long as their dose is&#xD;
                  stable for at least 4 weeks prior to initiating protocol therapy.&#xD;
&#xD;
               -  Participants must agree to not donate blood during the study or for 90 days after&#xD;
                  the last dose of study treatment&#xD;
&#xD;
               -  Female participant has a negative serum pregnancy test within 7 days prior to&#xD;
                  taking study treatment if of childbearing potential and agrees to abstain from&#xD;
                  activities that could result in pregnancy from screening through 180 days after&#xD;
                  the last dose of study treatment, or is of non-childbearing potential.&#xD;
                  Non-childbearing potential is defined as follows (by other than medical reasons):&#xD;
&#xD;
          -  ≥ 45 years of age and has not had menses for &gt;1 year&#xD;
&#xD;
          -  Patients who have been amenorrhoeic for &lt; 2 years without history of a hysterectomy&#xD;
             and oophorectomy must have a follicle stimulating hormone value in the postmenopausal&#xD;
             range upon screening evaluation&#xD;
&#xD;
          -  Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented&#xD;
             hysterectomy or oophorectomy must be confirmed with medical records of the actual&#xD;
             procedure or confirmed by imaging. Tubal ligation must be confirmed with medical&#xD;
             records of the actual procedure, otherwise the patient must be willing to use 2&#xD;
             adequate barrier methods throughout the study, starting with the screening visit&#xD;
             through 180 days after the last dose of study treatment. See below for a list of&#xD;
             acceptable birth control methods. Information must be captured appropriately within&#xD;
             the site's source documents. Note: Abstinence is acceptable if this is the established&#xD;
             and preferred contraception for the patient.&#xD;
&#xD;
          -  Birth Control: Participants of childbearing potential who are sexually active and&#xD;
             their partners must agree to the use of a highly effective form of contraception&#xD;
             throughout their participation beginning with time of consent, during the study&#xD;
             treatment and for 180 days after last dose of study treatment(s):&#xD;
&#xD;
               -  Combined (estrogen and progestogen containing) hormonal contraception associated&#xD;
                  with inhibition of ovulation:&#xD;
&#xD;
                    -  Oral route&#xD;
&#xD;
                    -  Intravaginal route&#xD;
&#xD;
                    -  Transdermal route&#xD;
&#xD;
               -  Progestogen-only hormonal contraception associated with inhibition of ovulation&#xD;
&#xD;
                    -  Oral&#xD;
&#xD;
                    -  Injectable&#xD;
&#xD;
                    -  Implantable&#xD;
&#xD;
               -  Intrauterine device&#xD;
&#xD;
               -  Intrauterine hormone-releasing system&#xD;
&#xD;
               -  Bilateral tubal occlusion&#xD;
&#xD;
               -  Vasectomized partner&#xD;
&#xD;
               -  Sexual abstinence, if the preferred and usual lifestyle of the subject&#xD;
&#xD;
                    -  Participant must agree to not breastfeed (or store breast milk for use)&#xD;
                       during the study or for 180 days afer the last dose of study treatment.&#xD;
&#xD;
                    -  Haemoglobin ≥8.5 g/dl (patients may not receive a transfusion within 4 weeks&#xD;
                       prior to initiating study treatment)&#xD;
&#xD;
                    -  Able to take oral medications&#xD;
&#xD;
                    -  Availability of archival ovarian cancer tissue from primary diagnosis&#xD;
                       (delivery of FFPE block or slides is prerequisite for randomisation)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who meet any of the following criteria will be excluded from study entry:&#xD;
&#xD;
               -  Ovarian tumours with low malignant potential (i.e. borderline tumours)&#xD;
&#xD;
               -  Any prior radiotherapy to the pelvis or abdomen, or any radiotherapy encompassing&#xD;
                  &gt; 20 % of the bone marrow within 2 weeks, or any radiotherapy within 1 week prior&#xD;
                  to Day 1 of protocol therapy&#xD;
&#xD;
               -  Surgery (including open biopsy and traumatic injury) within 4 weeks prior to&#xD;
                  first dose of Ganetespib, or anticipation of the need for major surgery during&#xD;
                  study treatment&#xD;
&#xD;
               -  Minor surgical procedures, within 24 hours prior to the first study treatment&#xD;
&#xD;
               -  Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).&#xD;
&#xD;
        Any serious, uncontrolled medical disorder, non-malignant systemic disease, or active,&#xD;
        uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular&#xD;
        arrhythmia, recent (within 90 days) myocardial infarction, chronic obstructive pulmonary&#xD;
        disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior&#xD;
        vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.&#xD;
&#xD;
          -  Current or recent (within 10 days prior to the first study drug dose) chronic daily&#xD;
             treatment with aspirin (&gt;325 mg/day).&#xD;
&#xD;
          -  Patients with a history of diagnosis, detection or treatment of any prior malignancies&#xD;
             ≤ 2 years prior to initiating protocol therapy, except: basal or squamous cell&#xD;
             carcinoma of the skin and cervical cancer that has been definitively treated.&#xD;
&#xD;
          -  Clinically significant gastro-intestinal (GI) tract abnormalities that may increase&#xD;
             the risk for GI bleeding and / or perforation including but not limited to: active&#xD;
             peptic ulcer disease, known intraluminal metastatic lesion/s with risk of bleeding;&#xD;
             inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), history of&#xD;
             bowel obstruction within 1 year prior to first study treatment (excluding&#xD;
             postoperative, i.e. within 4 weeks post surgery), other GI condition with increased&#xD;
             risk of perforation such as recurrence deeply infiltrating into the muscularis or&#xD;
             mucosa of the rectosigmoid or the mucosa of the bladder, or history of abdominal&#xD;
             fistula, gastrointestinal perforation or intra-abdominal abscess&#xD;
&#xD;
          -  Non-healing wound or non-healing bone fracture&#xD;
&#xD;
          -  Patients with symptomatic brain or leptomeningeal metastases (patients who are&#xD;
             asymptomatic since treatment of brain or leptomeningeal metastases, eg. after&#xD;
             irradiation, are eligible)&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) defined by ECHO below the institutional&#xD;
             lower limit of normal&#xD;
&#xD;
          -  Cerebrovascular accident (CVA)/ stroke or transient ischemic attack (TIA) or&#xD;
             sub-arachnoid haemorrhage within ≤ 6 months prior to first study treatment.&#xD;
&#xD;
          -  Significant cardiac disease: New York Heart Association (NYHA) Class 3 or 4;&#xD;
             myocardial infarction within the past 6 months; unstable angina; coronary angioplasty&#xD;
             or coronary atrial or ventricular cardiac arrhythmias&#xD;
&#xD;
          -  History of prolonged QT syndrome, or family member with prolonged QT syndrome&#xD;
&#xD;
          -  QTc interval &gt; 470 msec when 3 consecutive ECG values are averaged&#xD;
&#xD;
          -  Ventricular tachycardia or a supraventricular tachycardia that requires treatment with&#xD;
             a Class Ia antiarrhythmic drug (e.g. sotalol, amiodarone, dofetilide). Use of other&#xD;
             antiarrhythmic drugs is permitted&#xD;
&#xD;
          -  Second- or third-degree atrioventricular (AV) block, except: treated with a permanent&#xD;
             pacemaker Complete left bundle branch block (LBBB)&#xD;
&#xD;
          -  History of evidence of haemorrhagic disorders, patients with active bleeding or&#xD;
             pathologic conditions that carry high risk of bleeding, such as known bleeding&#xD;
             disorders, coagulopathy or tumour involving major vessels.&#xD;
&#xD;
          -  Participation in another clinical study with experimental therapy within 28 days&#xD;
             before start of treatment.&#xD;
&#xD;
          -  Participant must not be simultaneously enrolled in any interventional clinical trial.&#xD;
&#xD;
          -  Women who are pregnant or are lactating&#xD;
&#xD;
          -  Patients unable to be regularly followed for any reason (geographic, familiar, social,&#xD;
             psychologic, housed in an institution eg. prison because of a court agreement or&#xD;
             administrative order)&#xD;
&#xD;
          -  Subjects that are dependent on the sponsor/CRO or investigational site as well as on&#xD;
             the investigator.&#xD;
&#xD;
          -  History of known hypersensibility against any medication used in the study&#xD;
&#xD;
          -  Intolerance / Hypersensitivity reactions to components and excipients of study drugs&#xD;
&#xD;
          -  Peripheral neuropathy of grade &gt;2 per NCI CTCAE, version 4.03, within 4 weeks prior to&#xD;
             randomisation&#xD;
&#xD;
          -  Any other condition that, in the opinion of the investigator, may compromise the&#xD;
             safety, compliance of the patient, or would preclude the patient from successful&#xD;
             completion of the study&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Medical University of Innsbruck</name>
      <address>
        <city>Innsbruck</city>
        <zip>6020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZLeuven</name>
      <address>
        <city>Leuven</city>
        <state>Vlaams-Brabant</state>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre de lutte contre le cancer Francois Baclesse</name>
      <address>
        <city>Caen</city>
        <zip>14076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre anticancereux Leon Berard</name>
      <address>
        <city>Lyon</city>
        <zip>69008</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Assistance Publique Hôpitaux de Paris</name>
      <address>
        <city>Paris</city>
        <zip>75004</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Berlin Charité</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Bonn</name>
      <address>
        <city>Bonn</city>
        <zip>53127</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Dresden</name>
      <address>
        <city>Dresden</city>
        <zip>01069</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kliniken Essen Mitte, Evang. Huyssens- Stiftung/Knappschaft GmbH</name>
      <address>
        <city>Essen</city>
        <zip>45136</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Hamburg-Eppendorf</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Bologna</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Nazionale dei tumori Milano</name>
      <address>
        <city>Milan</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Università Cattolica del Sacro Cuore</name>
      <address>
        <city>Rome</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Belgium</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>December 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>September 14, 2023</last_update_submitted>
  <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ganetespib</keyword>
  <keyword>Niraparib</keyword>
  <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>
    <mesh_term>Fallopian Tube Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Niraparib</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03783949
org study id: 2017-004058-40
nct id: NCT03783949
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study will be performed in women with platinum-sensitive, high-grade serous, high-grade
      endometrioid, undifferentiated epithelial ovarian cancer, carcinosarcoma, fallopian tube or
      primary peritoneal cancer (proven by central histo-pathological review).

      A total of 120 subjects will be randomized (1:1:1) to three different treatment arms: (A)
      Standard arm (arm A): Carboplatin (AUC5 d1, q3w i.v.) in combination with Paclitaxel (175
      mg/m² d1, q3w i.v.) or Carboplatin (AUC4 d1, q3w i.v.) in combination with Gemcitabine (1000
      mg/m² d1, d8, q3w i.v.) followed by maintenance therapy with Niraparib (200/ 300 mg oral
      daily, q4w) // (B) First experimental arm (arm B): Ganetespib (150 mg/m2, d1, q3w) in
      combination with Carboplatin (AUC5 d1, q3w i.v.) followed by maintenance treatment with
      Niraparib (200/ 300 mg oral daily, q4w) // (C) Second experimental arm (arm C): Ganetespib
      (150 mg/m² d1, q3w i.v.) plus Carboplatin (AUC5 d1, q3w i.v.) followed by Ganetespib (100
      mg/m² d1, d8, d15, d22, q4w i.v.) and Niraparib (200 mg oral daily, q4w).

      Chemotherapy treatment will be given for 6 cycles, maintenance treatment with Ganetespib will
      be given for a maximum of 9 months or until disease progression, maintenance treatment with
      Niraparib can continue until disease progression.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Standard arm (arm A): Carboplatin (AUC5 d1, q3w i.v.) in combination with Paclitaxel (175 mg/m² d1, q3w i.v.) or Carboplatin (AUC4 d1, q3w i.v.) in combination with Gemcitabine (1000 mg/m² d1, d8, q3w i.v.) followed by maintenance therapy with Niraparib (200/ 300 mg oral daily, q4w) First experimental arm (arm B): Ganetespib (150 mg/m2, d1, q3w) in combination with Carboplatin (AUC5 d1, q3w i.v.) followed by maintenance treatment with Niraparib (200/ 300 mg oral daily, q4w) Second experimental arm (arm C): Ganetespib (150 mg/m² d1, q3w i.v.) plus Carboplatin (AUC5 d1, q3w i.v.) followed by Ganetespib (100 mg/m² d1, d8, d15, d22, q4w i.v.) and Niraparib (200 mg oral daily, q4w)
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival
time frame: 3 years 10 months
description: Progression-free survival (PFS) by RECIST 1.1
measure: Progression-free survival subgroup analysis
time frame: 3 years 10 months
description: Progression-free survival subgroup analysis
measure: Post-progression PFS (PFS2)
time frame: 3 years 10 months
description: Post-progression PFS (PFS2)
measure: Time to First Subsequent Therapy (TFST)
time frame: 3 years 10 months
description: Time to First Subsequent Therapy (TFST)
measure: Time to Second Subsequent Therapy (TSST)
time frame: 3 years 10 months
description: Time to Second Subsequent Therapy (TSST)
measure: Safety: Adverse events (AEs)
time frame: 3 years 10 months
description: Safety: Adverse events (AEs), measure according to NCI CTCAE, version 4.03
measure: Objective response rate (ORR)
time frame: 3 years 10 months
description: Objective response rate (ORR)
measure: Patients general health, functionality and well-being assessment using QLQ-C30 questionnaire
time frame: 3 years 10 months
description: Patient-reported outcome (PRO) questionnaire (QLQ-C30) will be used to assess patient's general health, functionality and well-being
measure: Overall survival (OS)
time frame: 3 years 10 months
description: Overall survival (OS)
measure: Patients general health, functionality and well-being assessment using QLQ-ov28 questionnaire
time frame: 3 years 10 months
description: Patient-reported outcome (PRO) questionnaire (QLQ-ov28) will be used to assess patient's general health, functionality and well-being
measure: Patients gastro-intestinal symptoms using Gastro-intestinal symptoms questionnaire
time frame: 3 years 10 months
description: Patient-reported outcome (PRO) questionnaire (gastro-intestinal symptoms) will be used to assess patient's gastro-intestinal symptoms
measure: Biomarker analysis
time frame: 3 years 10 months
description: Biomarker analysis on DNA level (e.g. free circulating tumour DNA)
measure: Biomarker analysis
time frame: 3 years 10 months
description: Biomarker analysis on RNA level
measure: Biomarker analysis
time frame: 3 years 10 months
description: Biomarker analysis on protein level (e.g. circulating tumour cells)
arm group label: Standard arm (arm A)
arm group type: Active Comparator
description: Carboplatin (AUC5 d1, q3w i.v.) in combination with Paclitaxel (175 mg/m² d1, q3w i.v.) or Carboplatin (AUC4 d1, q3w i.v.) in combination with Gemcitabine (1000 mg/m² d1, d8, q3w i.v.) followed by maintenance therapy with Niraparib (200/ 300 mg oral daily, q4w)
arm group label: First experimental arm (arm B)
arm group type: Experimental
description: Ganetespib (150 mg/m2, d1, q3w) in combination with Carboplatin (AUC5 d1, q3w i.v.) followed by maintenance treatment with Niraparib (200/ 300 mg oral daily, q4w)
arm group label: Second experimental arm (arm C)
arm group type: Experimental
description: Ganetespib (150 mg/m² d1, q3w i.v.) plus Carboplatin (AUC5 d1, q3w i.v.) followed by Ganetespib (100 mg/m² d1, d8, d15, d22, q4w i.v.) and Niraparib (200 mg oral daily, q4w)
intervention type: Drug
intervention name: Ganetespib
description: Ganetespib dose during chemotherapy will be 150mg/m² (q3w) Ganetespib dose during maintenance treatment will be 100mg/m² (q1w)
arm group label: First experimental arm (arm B)
arm group label: Second experimental arm (arm C)
intervention type: Drug
intervention name: Niraparib
description: Niraparib starting dose during maintenance treatment will be 200mg or 300mg depending on subject's body weight and subject neutrophil count (QD)
arm group label: First experimental arm (arm B)
arm group label: Second experimental arm (arm C)
arm group label: Standard arm (arm A)
intervention type: Drug
intervention name: Carboplatin
description: In combination with Gemcitabine: Carboplatin dose will be AUC4 (q3w) In combination with Paclitaxel: Carboplatin dose will be AUC5 (q3w)
arm group label: First experimental arm (arm B)
arm group label: Second experimental arm (arm C)
arm group label: Standard arm (arm A)
intervention type: Drug
intervention name: Paclitaxel
description: Paclitaxel dose will be 175mg/m² (q3w)
arm group label: Standard arm (arm A)
intervention type: Drug
intervention name: Gemcitabine
description: Gemcitabine dose will be 1000mg/m² (q3w, d1 & d8)
arm group label: Standard arm (arm A)
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Belgium
country: France
country: Germany
country: Italy
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Fallopian Tube Neoplasms
mesh term: Paclitaxel
mesh term: Carboplatin
mesh term: Gemcitabine
mesh term: Niraparib