<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/NCT01711541</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2012-02009</org_study_id>
    <secondary_id>NCI-2012-02009</secondary_id>
    <secondary_id>A091101</secondary_id>
    <secondary_id>A091101</secondary_id>
    <secondary_id>A091101</secondary_id>
    <secondary_id>N01CM62201</secondary_id>
    <secondary_id>U10CA180821</secondary_id>
    <secondary_id>U10CA031946</secondary_id>
    <nct_id>NCT01711541</nct_id>
  </id_info>
  <brief_title>Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IV Head and Neck Cancer</brief_title>
  <official_title>Carboplatin-Paclitaxel Induction Chemotherapy and ABT-888 (Veliparib) - a Phase 1/Randomized Phase 2 Study in Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This partially randomized phase I/II trial studies the side effects and best dose of&#xD;
      veliparib when given together with combination chemotherapy and to see how well they work in&#xD;
      treating patients with stage IV head and neck cancer. Drugs used in chemotherapy, such as&#xD;
      docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor&#xD;
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
      spreading. Veliparib may stop the growth of tumor cells by blocking some of the enzymes&#xD;
      needed for cell growth. It is not yet known whether combination chemotherapy is more&#xD;
      effective when given with or without veliparib in treating head and neck cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Determine the maximum tolerated dose (MTD), recommended phase II dose, dose limiting&#xD;
      toxicity (DLT), and safety of ABT-888 (veliparib) with carboplatin and paclitaxel induction&#xD;
      chemotherapy in locoregionally advanced head and neck (LAHNC) patients. (Phase I) II. Compare&#xD;
      magnitude of tumor shrinkage (response) following 2 cycles of induction chemotherapy with and&#xD;
      without ABT-888 in LAHNC. (Phase II)&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Compare progression-free (PFS), disease-specific (DSS), and overall survival (OS) in&#xD;
      subjects treated with or without ABT-888. (Phase II)&#xD;
&#xD;
      OUTLINE: This is a phase I, dose-escalation study of veliparib followed by a phase II study.&#xD;
&#xD;
      PHASE I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7, paclitaxel&#xD;
      intravenously (IV) over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes&#xD;
      on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression&#xD;
      or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.&#xD;
&#xD;
      PHASE II: Patients are randomized to 1 of 2 treatment arms.&#xD;
&#xD;
      ARM I: Patients receive veliparib, paclitaxel, and carboplatin as in Phase I. Treatment&#xD;
      repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable&#xD;
      toxicity. Within 10 days from completion of course 2, patients begin concomitant&#xD;
      chemoradiotherapy.&#xD;
&#xD;
      ARM II: Patients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and&#xD;
      carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of&#xD;
      disease progression or unacceptable toxicity. Within 10 days from completion of course 2,&#xD;
      patients begin concomitant chemoradiotherapy.&#xD;
&#xD;
      CONCOMITANT CHEMORADIOTHERAPY: Patients are assigned to 1 of 2 regimens of concomitant&#xD;
      chemoradiotherapy based on the guidelines of the institution where they are being treated.&#xD;
&#xD;
      OPTION I (CONCOMITANT CHEMORADIATION WITH CISPLATIN): Patients receive cisplatin IV on days 1&#xD;
      and 22 and undergo radiation therapy 5 days per week for 6 weeks. Treatment repeats every 2&#xD;
      weeks for 5 courses.&#xD;
&#xD;
      OPTION II (CONCOMITANT CHEMORADIATION WITH TFHX): Patients receive hydroxyurea PO every 12&#xD;
      hours on days 1-5 for up to 11 doses, fluorouracil IV over 120 hours on days 1-5, paclitaxel&#xD;
      IV on day 1, and undergo radiation therapy BID on days 1-5. Treatment repeats every 2 weeks&#xD;
      for 5 courses.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 2 weeks, 1, 3, 6, 12, 18,&#xD;
      24, 30, 36, 48, and 60 months. Patients who progress will be followed up every 6 months&#xD;
      through year 5.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 22, 2012</start_date>
  <completion_date type="Actual">May 15, 2023</completion_date>
  <primary_completion_date type="Actual">February 15, 2018</primary_completion_date>
  <phase>Phase 1/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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose Limiting Toxicity (Phase I)</measure>
    <time_frame>Up to 3 weeks</time_frame>
    <description>Dose Limiting Toxicity (DLTs) will be assessed during the first cycle of induction chemotherapy.&#xD;
The following events are considered DLTs: Grade 4 neutropenia (ANC &lt; 500) lasting more than 14 days, Febrile neutropenia, Grade 4 thrombocytopenia, dose delay of greater than 3 weeks due to failure to recover counts, treatment-related grade 3 or grade 4 non-hematological toxicity (excluding alopecia, fatigue, hypersensitivity reaction, nausea, vomiting, constipation, diarrhea, hypokalemia, hypomagnesemia, hypocalcemia, hypophosphatemia, and grade 3 hypertension), a dose delay of greater than 3 weeks for non-hematological toxicity despite replacement of electrolytes, maximum treatment for diarrhea, nausea, vomiting, and hypertension, any drug-related death.&#xD;
The number of patients reporting a DLT are reported below. The maximum tolerated dose (MTD) will be determined as the highest dose where 1 or fewer out of 6 patients reports a DLT.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Relative Change in Tumor Size as Measured by RECIST (Phase II)</measure>
    <time_frame>From baseline to 6 weeks</time_frame>
    <description>Treatment arms will be compared using the nonparametric Wilcoxon rank-sum test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Toxicity (Phase I and Phase II)</measure>
    <time_frame>upt to 5 years</time_frame>
    <description>Adverse Events were collected each cycle during treatment and follow-up according to the CTCAE v4.0 guidelines. The worst graded adverse event was determined for each patient. Below is a table of the number of patients that reported a Grade 3 or Grade 4 or Grade 5 as their worst reported event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS (Phase II)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free Survival (Phase II)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Local or Distant Progression (Phase II)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DSS (Phase II)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Summarized using cumulative incidence, and will be compared between groups using Gray's test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS (Phase II)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <condition>Stage IVA Oropharyngeal Carcinoma AJCC v7</condition>
  <condition>Stage IVB Oropharyngeal Carcinoma AJCC v7</condition>
  <arm_group>
    <arm_group_label>Arm I (veliparib, combination chemotherapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive veliparib PO BID on days 1-7, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (placebo, combination chemotherapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Within 10 days from completion of course 2, patients begin concomitant chemoradiotherapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (veliparib, combination chemotherapy)</arm_group_label>
    <arm_group_label>Arm II (placebo, combination chemotherapy)</arm_group_label>
    <other_name>Blastocarb</other_name>
    <other_name>Carboplat</other_name>
    <other_name>Carboplatin Hexal</other_name>
    <other_name>Carboplatino</other_name>
    <other_name>Carboplatinum</other_name>
    <other_name>Carbosin</other_name>
    <other_name>Carbosol</other_name>
    <other_name>Carbotec</other_name>
    <other_name>CBDCA</other_name>
    <other_name>Displata</other_name>
    <other_name>Ercar</other_name>
    <other_name>JM-8</other_name>
    <other_name>Nealorin</other_name>
    <other_name>Novoplatinum</other_name>
    <other_name>Paraplatin</other_name>
    <other_name>Paraplatin AQ</other_name>
    <other_name>Paraplatine</other_name>
    <other_name>Platinwas</other_name>
    <other_name>Ribocarbo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (veliparib, combination chemotherapy)</arm_group_label>
    <arm_group_label>Arm II (placebo, combination chemotherapy)</arm_group_label>
    <other_name>Abiplatin</other_name>
    <other_name>Blastolem</other_name>
    <other_name>Briplatin</other_name>
    <other_name>CDDP</other_name>
    <other_name>Cis-diammine-dichloroplatinum</other_name>
    <other_name>Cis-diamminedichloridoplatinum</other_name>
    <other_name>Cis-diamminedichloro Platinum (II)</other_name>
    <other_name>Cis-diamminedichloroplatinum</other_name>
    <other_name>Cis-dichloroammine Platinum (II)</other_name>
    <other_name>Cis-platinous Diamine Dichloride</other_name>
    <other_name>Cis-platinum</other_name>
    <other_name>Cis-platinum II</other_name>
    <other_name>Cis-platinum II Diamine Dichloride</other_name>
    <other_name>Cismaplat</other_name>
    <other_name>Cisplatina</other_name>
    <other_name>Cisplatinum</other_name>
    <other_name>Cisplatyl</other_name>
    <other_name>Citoplatino</other_name>
    <other_name>Citosin</other_name>
    <other_name>Cysplatyna</other_name>
    <other_name>DDP</other_name>
    <other_name>Lederplatin</other_name>
    <other_name>Metaplatin</other_name>
    <other_name>Neoplatin</other_name>
    <other_name>Peyrone's Chloride</other_name>
    <other_name>Peyrone's Salt</other_name>
    <other_name>Placis</other_name>
    <other_name>Plastistil</other_name>
    <other_name>Platamine</other_name>
    <other_name>Platiblastin</other_name>
    <other_name>Platiblastin-S</other_name>
    <other_name>Platinex</other_name>
    <other_name>Platinol</other_name>
    <other_name>Platinol- AQ</other_name>
    <other_name>Platinol-AQ</other_name>
    <other_name>Platinol-AQ VHA Plus</other_name>
    <other_name>Platinoxan</other_name>
    <other_name>Platinum</other_name>
    <other_name>Platinum Diamminodichloride</other_name>
    <other_name>Platiran</other_name>
    <other_name>Platistin</other_name>
    <other_name>Platosin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluorouracil</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (veliparib, combination chemotherapy)</arm_group_label>
    <arm_group_label>Arm II (placebo, combination chemotherapy)</arm_group_label>
    <other_name>5 Fluorouracil</other_name>
    <other_name>5 Fluorouracilum</other_name>
    <other_name>5 FU</other_name>
    <other_name>5-Fluoro-2,4(1H, 3H)-pyrimidinedione</other_name>
    <other_name>5-Fluorouracil</other_name>
    <other_name>5-Fluracil</other_name>
    <other_name>5-Fu</other_name>
    <other_name>5FU</other_name>
    <other_name>AccuSite</other_name>
    <other_name>Carac</other_name>
    <other_name>Fluoro Uracil</other_name>
    <other_name>Fluouracil</other_name>
    <other_name>Flurablastin</other_name>
    <other_name>Fluracedyl</other_name>
    <other_name>Fluracil</other_name>
    <other_name>Fluril</other_name>
    <other_name>Fluroblastin</other_name>
    <other_name>Ribofluor</other_name>
    <other_name>Ro 2-9757</other_name>
    <other_name>Ro-2-9757</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxyurea</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (veliparib, combination chemotherapy)</arm_group_label>
    <arm_group_label>Arm II (placebo, combination chemotherapy)</arm_group_label>
    <other_name>Droxia</other_name>
    <other_name>Hydrea</other_name>
    <other_name>Hydroxycarbamide</other_name>
    <other_name>Litalir</other_name>
    <other_name>Onco-Carbide</other_name>
    <other_name>Oncocarbide</other_name>
    <other_name>Oxeron</other_name>
    <other_name>SQ 1089</other_name>
    <other_name>SQ-1089</other_name>
    <other_name>Syrea</other_name>
    <other_name>WR 83799</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (veliparib, combination chemotherapy)</arm_group_label>
    <arm_group_label>Arm II (placebo, combination chemotherapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (veliparib, combination chemotherapy)</arm_group_label>
    <arm_group_label>Arm II (placebo, combination chemotherapy)</arm_group_label>
    <other_name>Anzatax</other_name>
    <other_name>Asotax</other_name>
    <other_name>Bristaxol</other_name>
    <other_name>Praxel</other_name>
    <other_name>Taxol</other_name>
    <other_name>Taxol Konzentrat</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo Administration</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm II (placebo, combination chemotherapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation Therapy</intervention_name>
    <description>Undergo radiation therapy</description>
    <arm_group_label>Arm I (veliparib, combination chemotherapy)</arm_group_label>
    <arm_group_label>Arm II (placebo, combination chemotherapy)</arm_group_label>
    <other_name>Cancer Radiotherapy</other_name>
    <other_name>Energy Type</other_name>
    <other_name>ENERGY_TYPE</other_name>
    <other_name>Irradiate</other_name>
    <other_name>Irradiated</other_name>
    <other_name>Irradiation</other_name>
    <other_name>Name of Radiation Therapy Course</other_name>
    <other_name>Radiation</other_name>
    <other_name>Radiation Therapy, NOS</other_name>
    <other_name>Radiotherapeutics</other_name>
    <other_name>Radiotherapy</other_name>
    <other_name>RT</other_name>
    <other_name>Therapy, Radiation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Veliparib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (veliparib, combination chemotherapy)</arm_group_label>
    <other_name>ABT-888</other_name>
    <other_name>PARP-1 inhibitor ABT-888</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  PHASE I:&#xD;
&#xD;
          -  Patients who are treatment naïve, high risk, stage IVa/IVb (all other sites) and&#xD;
             histologically proven squamous cell carcinoma of the head and neck (SCCHN) with no&#xD;
             definitive evidence of metastatic disease, excluding patients with oropharynx human&#xD;
             papillomavirus (HPV)-positive tumors; in summary, those patients eligible are newly&#xD;
             diagnosed and treatment naive:&#xD;
&#xD;
               -  Stage IVa-b squamous cell carcinoma other than oropharyngeal cancer (OPC), or&#xD;
&#xD;
               -  Oropharyngeal cancer (OPC) HPV-negative, stage IVa-b&#xD;
&#xD;
          -  PHASE II:&#xD;
&#xD;
          -  Patients who are treatment naïve, high risk, stage IVa/IVb (all other sites)&#xD;
             histologically proven SCCHN with no definitive evidence of metastatic disease; in&#xD;
             summary, those patients eligible are:&#xD;
&#xD;
               -  Stage IVa-b SCCHN other than OPC, or&#xD;
&#xD;
               -  OPC, HPV-negative, IVa-b, or&#xD;
&#xD;
               -  OPC, HPV positive, with greater than 10 pack-year smoking history and N2b-N3&#xD;
                  disease&#xD;
&#xD;
          -  PHASE I AND II:&#xD;
&#xD;
          -  Patients must have at least one measurable site of disease according to Response&#xD;
             Evaluation Criteria in Solid Tumors (RECIST) criteria; i.e., patients must have&#xD;
             measurable disease, defined as at least one lesion that can be accurately measured in&#xD;
             at least one dimension (longest diameter to be recorded for non-nodal lesions and&#xD;
             short axis for nodal lesions) as &gt;= 20 mm with conventional techniques or as &gt;= 10 mm&#xD;
             with spiral computed tomography (CT) scan magnetic resonance imaging (MRI), or&#xD;
             calipers by clinical exam&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1&#xD;
&#xD;
          -  Patients must be able to swallow the drug&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/mm^3&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/mm^3&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mm^3&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 institutional upper limit of normal (ULN)&#xD;
&#xD;
          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and&#xD;
             serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =&lt; 2.5 x&#xD;
             institutional ULN as calculated by Cockcroft-Gault&#xD;
&#xD;
          -  Creatinine clearance &gt;= 60 mL/min/1.73 m^2 for patients with creatinine levels above&#xD;
             ULN as calculated by Cockcroft-Gault&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents are not eligible&#xD;
&#xD;
          -  Patients with active seizure or a history of seizure are not eligible&#xD;
&#xD;
          -  Patients with a history of allergic reactions attributed to compounds of similar&#xD;
             chemical or biologic composition to ABT-888 or other agents used in study, including&#xD;
             Cremophor, carboplatin, paclitaxel, cisplatin, 5-fluorouracil, hydroxyurea, or any&#xD;
             compounds of similar chemical or biologic composition are not eligible&#xD;
&#xD;
          -  Patients with impairment of gastrointestinal function or gastrointestinal disease that&#xD;
             may significantly alter the absorption of ABT-888 (e.g., ulcerative disease,&#xD;
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel&#xD;
             resection) are not eligible to participate in this study&#xD;
&#xD;
          -  Patients with uncontrolled intercurrent illness including, but not limited to, ongoing&#xD;
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             cardiac arrhythmia, or psychiatric illness/social situations that would limit&#xD;
             compliance with study requirements are not eligible to participate in the study&#xD;
&#xD;
          -  Pregnant women are not eligible to participate in this study; NOTE: women of child&#xD;
             bearing potential must have a negative serum or urine pregnancy test within 7 days&#xD;
             prior to treatment&#xD;
&#xD;
               -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
                  (hormonal or barrier method of birth control; abstinence) prior to study entry&#xD;
                  and for the duration of study participation; should a woman become pregnant or&#xD;
                  suspect she is pregnant while she or her partner is participating in this study,&#xD;
                  she should inform her treating physician immediately;&#xD;
&#xD;
               -  Breastfeeding should be discontinued if the mother is treated with ABT-888&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral&#xD;
             therapy are not eligible&#xD;
&#xD;
          -  Patients receiving chronic, systemic treatment with corticosteroids or another&#xD;
             immunosuppressive agent are not eligible to participate in this study; topical or&#xD;
             inhaled corticosteroids are allowed&#xD;
&#xD;
          -  Patients with other malignancies within the past 2 years, except for adequately&#xD;
             treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin or&#xD;
             surgically treated early stage solid tumors are ineligible to participate in this&#xD;
             study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jonas De Souza</last_name>
    <role>Principal Investigator</role>
    <affiliation>Alliance for Clinical Trials in Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Comprehensive Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NorthShore University HealthSystem-Evanston Hospital</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNC Lineberger Comprehensive Cancer Center</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>October 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <results_first_submitted>March 20, 2019</results_first_submitted>
  <results_first_submitted_qc>May 15, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 5, 2019</results_first_posted>
  <last_update_submitted>June 6, 2023</last_update_submitted>
  <last_update_submitted_qc>June 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2023</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>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Oropharyngeal 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>Cisplatin</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
    <mesh_term>Hydroxyurea</mesh_term>
    <mesh_term>Veliparib</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 11, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT01711541/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>The study originally opened at Dose Level 0 with a treatment of Docetaxel, cisplatin and flouricil (TPF) in combination with ABT-888 (veliparib). With a concern for the feasibility of this regimen in other reported studies, this study was suspended and re-opened with a treatment of Carboplatin and Paclitaxel in combination with ABT-888.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Dose Level 0</title>
          <description>ABT-888 doses will be given at 200 mg bid for 7 days in combination with TPF Induction</description>
        </group>
        <group group_id="P2">
          <title>Dose Level 0B</title>
          <description>ABT-888 doses will be given at 200 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
        </group>
        <group group_id="P3">
          <title>Dose Level 1</title>
          <description>ABT-888 doses will be given at 250 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
        </group>
        <group group_id="P4">
          <title>Dose Level 2</title>
          <description>ABT-888 doses will be given at 300 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
        </group>
        <group group_id="P5">
          <title>Dose Level 3</title>
          <description>ABT-888 doses will be given at 350 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Cancel prior to treatment</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 group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ineligible</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Dose Level 0</title>
          <description>ABT-888 doses will be given at 200 mg bid for 7 days in combination with TPF Induction</description>
        </group>
        <group group_id="B2">
          <title>Dose Level 0B</title>
          <description>ABT-888 doses will be given at 200 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
        </group>
        <group group_id="B3">
          <title>Dose Level 1</title>
          <description>ABT-888 doses will be given at 250 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
        </group>
        <group group_id="B4">
          <title>Dose Level 2</title>
          <description>ABT-888 doses will be given at 300 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
        </group>
        <group group_id="B5">
          <title>Dose Level 3</title>
          <description>ABT-888 doses will be given at 350 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
        </group>
        <group group_id="B6">
          <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="4"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="3"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="7"/>
            <count group_id="B6" value="24"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="72.5" lower_limit="59" upper_limit="81"/>
                    <measurement group_id="B2" value="62.5" lower_limit="24" upper_limit="64"/>
                    <measurement group_id="B3" value="67" lower_limit="47" upper_limit="67"/>
                    <measurement group_id="B4" value="63.5" lower_limit="40" upper_limit="75"/>
                    <measurement group_id="B5" value="61" lower_limit="58" upper_limit="69"/>
                    <measurement group_id="B6" value="63.5" lower_limit="24" upper_limit="81"/>
                  </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="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <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 group_id="B6" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="7"/>
                    <measurement group_id="B6" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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 group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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 group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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 group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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 group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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="1"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="7"/>
                    <measurement group_id="B6" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Dose Limiting Toxicity (Phase I)</title>
        <description>Dose Limiting Toxicity (DLTs) will be assessed during the first cycle of induction chemotherapy.&#xD;
The following events are considered DLTs: Grade 4 neutropenia (ANC &lt; 500) lasting more than 14 days, Febrile neutropenia, Grade 4 thrombocytopenia, dose delay of greater than 3 weeks due to failure to recover counts, treatment-related grade 3 or grade 4 non-hematological toxicity (excluding alopecia, fatigue, hypersensitivity reaction, nausea, vomiting, constipation, diarrhea, hypokalemia, hypomagnesemia, hypocalcemia, hypophosphatemia, and grade 3 hypertension), a dose delay of greater than 3 weeks for non-hematological toxicity despite replacement of electrolytes, maximum treatment for diarrhea, nausea, vomiting, and hypertension, any drug-related death.&#xD;
The number of patients reporting a DLT are reported below. The maximum tolerated dose (MTD) will be determined as the highest dose where 1 or fewer out of 6 patients reports a DLT.</description>
        <time_frame>Up to 3 weeks</time_frame>
        <population>Dose Level 0 was not included in this outcome due to a change in treatment regimen. On Dose Level 0B, 1 patient was ineligible based on protocol criteria. On dose level 2, 1 patient cancelled prior to treatment, 1 had a dosing error and 1 pt did not complete cycle 1. On Dose Level 3, 1 patient cancelled prior to treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0</title>
            <description>ABT-888 doses will be given at 200 mg bid for 7 days in combination with TPF induction.</description>
          </group>
          <group group_id="O2">
            <title>Dose Level 0B</title>
            <description>ABT-888 doses will be given at 200 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
          </group>
          <group group_id="O3">
            <title>Dose Level 1</title>
            <description>ABT-888 doses will be given at 250 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
          </group>
          <group group_id="O4">
            <title>Dose Level 2</title>
            <description>ABT-888 doses will be given at 300 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
          </group>
          <group group_id="O5">
            <title>Dose Level 3</title>
            <description>ABT-888 doses will be given at 350 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Dose Limiting Toxicity (Phase I)</title>
          <description>Dose Limiting Toxicity (DLTs) will be assessed during the first cycle of induction chemotherapy.&#xD;
The following events are considered DLTs: Grade 4 neutropenia (ANC &lt; 500) lasting more than 14 days, Febrile neutropenia, Grade 4 thrombocytopenia, dose delay of greater than 3 weeks due to failure to recover counts, treatment-related grade 3 or grade 4 non-hematological toxicity (excluding alopecia, fatigue, hypersensitivity reaction, nausea, vomiting, constipation, diarrhea, hypokalemia, hypomagnesemia, hypocalcemia, hypophosphatemia, and grade 3 hypertension), a dose delay of greater than 3 weeks for non-hematological toxicity despite replacement of electrolytes, maximum treatment for diarrhea, nausea, vomiting, and hypertension, any drug-related death.&#xD;
The number of patients reporting a DLT are reported below. The maximum tolerated dose (MTD) will be determined as the highest dose where 1 or fewer out of 6 patients reports a DLT.</description>
          <population>Dose Level 0 was not included in this outcome due to a change in treatment regimen. On Dose Level 0B, 1 patient was ineligible based on protocol criteria. On dose level 2, 1 patient cancelled prior to treatment, 1 had a dosing error and 1 pt did not complete cycle 1. On Dose Level 3, 1 patient cancelled prior to treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Relative Change in Tumor Size as Measured by RECIST (Phase II)</title>
        <description>Treatment arms will be compared using the nonparametric Wilcoxon rank-sum test.</description>
        <time_frame>From baseline to 6 weeks</time_frame>
        <population>The Phase II portion of this study never opened and no analysis was planned.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Veliparib, Combination Chemotherapy)</title>
            <description>Patients receive veliparib PO BID on days 1-7, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.&#xD;
Carboplatin: Given IV&#xD;
Cisplatin: Given IV&#xD;
Fluorouracil: Given IV&#xD;
Hydroxyurea: Given PO&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
Radiation Therapy: Undergo radiation therapy&#xD;
Veliparib: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Combination Chemotherapy)</title>
            <description>Patients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Within 10 days from completion of course 2, patients begin concomitant chemoradiotherapy.&#xD;
Carboplatin: Given IV&#xD;
Cisplatin: Given IV&#xD;
Fluorouracil: Given IV&#xD;
Hydroxyurea: Given PO&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Paclitaxel: Given IV&#xD;
Placebo: Given PO&#xD;
Radiation Therapy: Undergo radiation therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Relative Change in Tumor Size as Measured by RECIST (Phase II)</title>
          <description>Treatment arms will be compared using the nonparametric Wilcoxon rank-sum test.</description>
          <population>The Phase II portion of this study never opened and no analysis was planned.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Toxicity (Phase I and Phase II)</title>
        <description>Adverse Events were collected each cycle during treatment and follow-up according to the CTCAE v4.0 guidelines. The worst graded adverse event was determined for each patient. Below is a table of the number of patients that reported a Grade 3 or Grade 4 or Grade 5 as their worst reported event.</description>
        <time_frame>upt to 5 years</time_frame>
        <population>All patients that started protocol treatment and were evaluated for adverse events are included in this analysis. The Phase II portion of the study never opened, and therefore no data was collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0</title>
            <description>ABT-888 doses will be given at 200 mg bid for 7 days in combination with TPF Induction.</description>
          </group>
          <group group_id="O2">
            <title>Dose Level 0B</title>
            <description>ABT-888 doses will be given at 200 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
          </group>
          <group group_id="O3">
            <title>Dose Level 1</title>
            <description>ABT-888 doses will be given at 250 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
          </group>
          <group group_id="O4">
            <title>Dose Level 2</title>
            <description>ABT-888 doses will be given at 300 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
          </group>
          <group group_id="O5">
            <title>Dose Level 3</title>
            <description>ABT-888 doses will be given at 350 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Toxicity (Phase I and Phase II)</title>
          <description>Adverse Events were collected each cycle during treatment and follow-up according to the CTCAE v4.0 guidelines. The worst graded adverse event was determined for each patient. Below is a table of the number of patients that reported a Grade 3 or Grade 4 or Grade 5 as their worst reported event.</description>
          <population>All patients that started protocol treatment and were evaluated for adverse events are included in this analysis. The Phase II portion of the study never opened, and therefore no data was collected.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 3 Adverse Event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="4"/>
                    <measurement group_id="O5" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 Adverse Event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 Adverse Event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PFS (Phase II)</title>
        <description>Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
        <time_frame>Up to 5 years</time_frame>
        <population>No patients were eligible for this Phase II endpoint. The Phase II portion of this study never opened.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Veliparib, Combination Chemotherapy)</title>
            <description>Patients receive veliparib PO BID on days 1-7, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Combination Chemotherapy)</title>
            <description>Patients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Within 10 days from completion of course 2, patients begin concomitant chemoradiotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>PFS (Phase II)</title>
          <description>Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
          <population>No patients were eligible for this Phase II endpoint. The Phase II portion of this study never opened.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease-free Survival (Phase II)</title>
        <description>Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
        <time_frame>Up to 5 years</time_frame>
        <population>No patients were eligible for this Phase II endpoint. The Phase II portion of this study never opened.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Veliparib, Combination Chemotherapy)</title>
            <description>Patients receive veliparib PO BID on days 1-7, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Combination Chemotherapy)</title>
            <description>Patients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Within 10 days from completion of course 2, patients begin concomitant chemoradiotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease-free Survival (Phase II)</title>
          <description>Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
          <population>No patients were eligible for this Phase II endpoint. The Phase II portion of this study never opened.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Local or Distant Progression (Phase II)</title>
        <description>Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
        <time_frame>Up to 5 years</time_frame>
        <population>No patients were eligible for this Phase II endpoint. The Phase II portion of this study never opened.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Veliparib, Combination Chemotherapy)</title>
            <description>Patients receive veliparib PO BID on days 1-7, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Combination Chemotherapy)</title>
            <description>Patients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Within 10 days from completion of course 2, patients begin concomitant chemoradiotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Local or Distant Progression (Phase II)</title>
          <description>Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
          <population>No patients were eligible for this Phase II endpoint. The Phase II portion of this study never opened.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DSS (Phase II)</title>
        <description>Summarized using cumulative incidence, and will be compared between groups using Gray's test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
        <time_frame>Up to 5 years</time_frame>
        <population>No patients were eligible for this Phase II endpoint. The Phase II portion of this study never opened.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Veliparib, Combination Chemotherapy)</title>
            <description>Patients receive veliparib PO BID on days 1-7, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Combination Chemotherapy)</title>
            <description>Patients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Within 10 days from completion of course 2, patients begin concomitant chemoradiotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>DSS (Phase II)</title>
          <description>Summarized using cumulative incidence, and will be compared between groups using Gray's test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
          <population>No patients were eligible for this Phase II endpoint. The Phase II portion of this study never opened.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>OS (Phase II)</title>
        <description>Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
        <time_frame>Up to 5 years</time_frame>
        <population>No patients were eligible for this Phase II endpoint. The Phase II portion of this study never opened.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Veliparib, Combination Chemotherapy)</title>
            <description>Patients receive veliparib PO BID on days 1-7, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Combination Chemotherapy)</title>
            <description>Patients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Within 10 days from completion of course 2, patients begin concomitant chemoradiotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>OS (Phase II)</title>
          <description>Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.</description>
          <population>No patients were eligible for this Phase II endpoint. The Phase II portion of this study never opened.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected every week during treatment (up to 13 weeks) and then every 6 months during clinical follow-up for a maximum of 5 years from registration.</time_frame>
      <desc>Adverse events were collected every week during treatment (up to 13 weeks) and then every 6 months during clinical follow-up for a maximum of 5 years from registration. All patients that began study treatment and were assessed for adverse events are included in this analysis. Patients that cancelled or were not evaluated for adverse events were not included.</desc>
      <group_list>
        <group group_id="E1">
          <title>Dose Level 0</title>
          <description>ABT-888 doses will be given at 200 mg bid for 7 days in combination with TPF Induction.</description>
        </group>
        <group group_id="E2">
          <title>Dose Level 0B</title>
          <description>ABT-888 doses will be given at 200 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
        </group>
        <group group_id="E3">
          <title>Dose Level 1</title>
          <description>ABT-888 doses will be given at 250 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
        </group>
        <group group_id="E4">
          <title>Dose Level 2</title>
          <description>ABT-888 doses will be given at 300 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
        </group>
        <group group_id="E5">
          <title>Dose Level 3</title>
          <description>ABT-888 doses will be given at 350 mg bid for 7 days in combination with paclitaxel 100 mg/m2 and carboplatin AUC 6.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 12</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Acidosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchopulmonary hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pulmonary edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 12</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="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="7" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="10" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="10" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E5" events="30" subjects_affected="7" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Left ventricular systolic dysfunction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear and labyrinth disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="5" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="4" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="10" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="6" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="9" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E5" events="4" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="14" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="7" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="5" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" events="12" subjects_affected="4" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="24" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="12" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="22" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="23" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E5" events="24" subjects_affected="4" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="8" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="10" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" events="9" subjects_affected="5" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Oral hemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="5" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="10" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="12" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="19" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="13" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="16" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="10" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E5" events="29" subjects_affected="7" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" events="13" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="10" subjects_affected="4" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Catheter related infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Dermatitis radiation</sub_title>
                <counts group_id="E1" events="15" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="14" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="9" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E5" events="10" subjects_affected="4" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Injury, poisoning and procedural complications - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Tracheostomy site bleeding</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="21" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="16" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" events="4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="20" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="7" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E5" events="4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="5" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>INR increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="17" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="5" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" events="23" subjects_affected="6" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="6" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="5" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="8" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E5" events="18" subjects_affected="6" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="11" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="14" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="28" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E5" events="16" subjects_affected="7" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" events="6" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E5" events="21" subjects_affected="6" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="11" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="5" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="12" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="17" subjects_affected="5" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="7" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="7" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="11" subjects_affected="4" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="6" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Trismus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Aphonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="5" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="10" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="6" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="11" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="12" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="10" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" events="15" subjects_affected="4" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="8" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="6" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Laryngeal hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Laryngeal inflammation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="7" subjects_affected="4" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Voice alteration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" events="5" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Erythema multiforme</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="5" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Skin hyperpigmentation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </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 only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Everett E. Vokes, M.D.</name_or_title>
      <organization>Alliance for Clinical Trials in Oncology</organization>
      <phone>773-702-9306</phone>
      <email>evokes@medicine.bsd.uchicago.edu</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/NCT01711541
org study id: NCI-2012-02009
secondary id: NCI-2012-02009
secondary id: A091101
secondary id: A091101
secondary id: A091101
secondary id: N01CM62201
secondary id: U10CA180821
secondary id: U10CA031946
nct id: NCT01711541
lead sponsor: 
has dmc: No
This partially randomized phase I/II trial studies the side effects and best dose of
      veliparib when given together with combination chemotherapy and to see how well they work in
      treating patients with stage IV head and neck cancer. Drugs used in chemotherapy, such as
      docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Veliparib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. It is not yet known whether combination chemotherapy is more
      effective when given with or without veliparib in treating head and neck cancer.
PRIMARY OBJECTIVES:

      I. Determine the maximum tolerated dose (MTD), recommended phase II dose, dose limiting
      toxicity (DLT), and safety of ABT-888 (veliparib) with carboplatin and paclitaxel induction
      chemotherapy in locoregionally advanced head and neck (LAHNC) patients. (Phase I) II. Compare
      magnitude of tumor shrinkage (response) following 2 cycles of induction chemotherapy with and
      without ABT-888 in LAHNC. (Phase II)

      SECONDARY OBJECTIVES:

      I. Compare progression-free (PFS), disease-specific (DSS), and overall survival (OS) in
      subjects treated with or without ABT-888. (Phase II)

      OUTLINE: This is a phase I, dose-escalation study of veliparib followed by a phase II study.

      PHASE I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7, paclitaxel
      intravenously (IV) over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes
      on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression
      or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.

      PHASE II: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive veliparib, paclitaxel, and carboplatin as in Phase I. Treatment
      repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable
      toxicity. Within 10 days from completion of course 2, patients begin concomitant
      chemoradiotherapy.

      ARM II: Patients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and
      carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of
      disease progression or unacceptable toxicity. Within 10 days from completion of course 2,
      patients begin concomitant chemoradiotherapy.

      CONCOMITANT CHEMORADIOTHERAPY: Patients are assigned to 1 of 2 regimens of concomitant
      chemoradiotherapy based on the guidelines of the institution where they are being treated.

      OPTION I (CONCOMITANT CHEMORADIATION WITH CISPLATIN): Patients receive cisplatin IV on days 1
      and 22 and undergo radiation therapy 5 days per week for 6 weeks. Treatment repeats every 2
      weeks for 5 courses.

      OPTION II (CONCOMITANT CHEMORADIATION WITH TFHX): Patients receive hydroxyurea PO every 12
      hours on days 1-5 for up to 11 doses, fluorouracil IV over 120 hours on days 1-5, paclitaxel
      IV on day 1, and undergo radiation therapy BID on days 1-5. Treatment repeats every 2 weeks
      for 5 courses.

      After completion of study treatment, patients are followed up at 2 weeks, 1, 3, 6, 12, 18,
      24, 30, 36, 48, and 60 months. Patients who progress will be followed up every 6 months
      through year 5.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Dose Limiting Toxicity (Phase I)
time frame: Up to 3 weeks
description: Dose Limiting Toxicity (DLTs) will be assessed during the first cycle of induction chemotherapy.
The following events are considered DLTs: Grade 4 neutropenia (ANC < 500) lasting more than 14 days, Febrile neutropenia, Grade 4 thrombocytopenia, dose delay of greater than 3 weeks due to failure to recover counts, treatment-related grade 3 or grade 4 non-hematological toxicity (excluding alopecia, fatigue, hypersensitivity reaction, nausea, vomiting, constipation, diarrhea, hypokalemia, hypomagnesemia, hypocalcemia, hypophosphatemia, and grade 3 hypertension), a dose delay of greater than 3 weeks for non-hematological toxicity despite replacement of electrolytes, maximum treatment for diarrhea, nausea, vomiting, and hypertension, any drug-related death.
The number of patients reporting a DLT are reported below. The maximum tolerated dose (MTD) will be determined as the highest dose where 1 or fewer out of 6 patients reports a DLT.
measure: Relative Change in Tumor Size as Measured by RECIST (Phase II)
time frame: From baseline to 6 weeks
description: Treatment arms will be compared using the nonparametric Wilcoxon rank-sum test.
measure: Toxicity (Phase I and Phase II)
time frame: upt to 5 years
description: Adverse Events were collected each cycle during treatment and follow-up according to the CTCAE v4.0 guidelines. The worst graded adverse event was determined for each patient. Below is a table of the number of patients that reported a Grade 3 or Grade 4 or Grade 5 as their worst reported event.
measure: PFS (Phase II)
time frame: Up to 5 years
description: Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.
measure: Disease-free Survival (Phase II)
time frame: Up to 5 years
description: Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.
measure: Time to Local or Distant Progression (Phase II)
time frame: Up to 5 years
description: Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.
measure: DSS (Phase II)
time frame: Up to 5 years
description: Summarized using cumulative incidence, and will be compared between groups using Gray's test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.
measure: OS (Phase II)
time frame: Up to 5 years
description: Summarized using the method of Kaplan-Meier, and compared between groups using the log-rank test. Multivariate Cox proportional hazards regression models will be used to further explore group differences adjusting for other prognostic factors, as well as to estimate hazard ratios.
arm group label: Arm I (veliparib, combination chemotherapy)
arm group type: Experimental
description: Patients receive veliparib PO BID on days 1-7, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then continue on to concomitant chemoradiotherapy.
arm group label: Arm II (placebo, combination chemotherapy)
arm group type: Experimental
description: Patients receive placebo PO BID on days 1-7. Patients also receive paclitaxel and carboplatin as in Phase I. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Within 10 days from completion of course 2, patients begin concomitant chemoradiotherapy.
intervention type: Drug
intervention name: Carboplatin
description: Given IV
arm group label: Arm I (veliparib, combination chemotherapy)
arm group label: Arm II (placebo, combination chemotherapy)
other name: Blastocarb
other name: Carboplat
other name: Carboplatin Hexal
other name: Carboplatino
other name: Carboplatinum
other name: Carbosin
other name: Carbosol
other name: Carbotec
other name: CBDCA
other name: Displata
other name: Ercar
other name: JM-8
other name: Nealorin
other name: Novoplatinum
other name: Paraplatin
other name: Paraplatin AQ
other name: Paraplatine
other name: Platinwas
other name: Ribocarbo
intervention type: Drug
intervention name: Cisplatin
description: Given IV
arm group label: Arm I (veliparib, combination chemotherapy)
arm group label: Arm II (placebo, combination chemotherapy)
other name: Abiplatin
other name: Blastolem
other name: Briplatin
other name: CDDP
other name: Cis-diammine-dichloroplatinum
other name: Cis-diamminedichloridoplatinum
other name: Cis-diamminedichloro Platinum (II)
other name: Cis-diamminedichloroplatinum
other name: Cis-dichloroammine Platinum (II)
other name: Cis-platinous Diamine Dichloride
other name: Cis-platinum
other name: Cis-platinum II
other name: Cis-platinum II Diamine Dichloride
other name: Cismaplat
other name: Cisplatina
other name: Cisplatinum
other name: Cisplatyl
other name: Citoplatino
other name: Citosin
other name: Cysplatyna
other name: DDP
other name: Lederplatin
other name: Metaplatin
other name: Neoplatin
other name: Peyrone's Chloride
other name: Peyrone's Salt
other name: Placis
other name: Plastistil
other name: Platamine
other name: Platiblastin
other name: Platiblastin-S
other name: Platinex
other name: Platinol
other name: Platinol- AQ
other name: Platinol-AQ
other name: Platinol-AQ VHA Plus
other name: Platinoxan
other name: Platinum
other name: Platinum Diamminodichloride
other name: Platiran
other name: Platistin
other name: Platosin
intervention type: Drug
intervention name: Fluorouracil
description: Given IV
arm group label: Arm I (veliparib, combination chemotherapy)
arm group label: Arm II (placebo, combination chemotherapy)
other name: 5 Fluorouracil
other name: 5 Fluorouracilum
other name: 5 FU
other name: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
other name: 5-Fluorouracil
other name: 5-Fluracil
other name: 5-Fu
other name: 5FU
other name: AccuSite
other name: Carac
other name: Fluoro Uracil
other name: Fluouracil
other name: Flurablastin
other name: Fluracedyl
other name: Fluracil
other name: Fluril
other name: Fluroblastin
other name: Ribofluor
other name: Ro 2-9757
other name: Ro-2-9757
intervention type: Drug
intervention name: Hydroxyurea
description: Given PO
arm group label: Arm I (veliparib, combination chemotherapy)
arm group label: Arm II (placebo, combination chemotherapy)
other name: Droxia
other name: Hydrea
other name: Hydroxycarbamide
other name: Litalir
other name: Onco-Carbide
other name: Oncocarbide
other name: Oxeron
other name: SQ 1089
other name: SQ-1089
other name: Syrea
other name: WR 83799
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm I (veliparib, combination chemotherapy)
arm group label: Arm II (placebo, combination chemotherapy)
intervention type: Drug
intervention name: Paclitaxel
description: Given IV
arm group label: Arm I (veliparib, combination chemotherapy)
arm group label: Arm II (placebo, combination chemotherapy)
other name: Anzatax
other name: Asotax
other name: Bristaxol
other name: Praxel
other name: Taxol
other name: Taxol Konzentrat
intervention type: Other
intervention name: Placebo Administration
description: Given PO
arm group label: Arm II (placebo, combination chemotherapy)
intervention type: Radiation
intervention name: Radiation Therapy
description: Undergo radiation therapy
arm group label: Arm I (veliparib, combination chemotherapy)
arm group label: Arm II (placebo, combination chemotherapy)
other name: Cancer Radiotherapy
other name: Energy Type
other name: ENERGY_TYPE
other name: Irradiate
other name: Irradiated
other name: Irradiation
other name: Name of Radiation Therapy Course
other name: Radiation
other name: Radiation Therapy, NOS
other name: Radiotherapeutics
other name: Radiotherapy
other name: RT
other name: Therapy, Radiation
intervention type: Drug
intervention name: Veliparib
description: Given PO
arm group label: Arm I (veliparib, combination chemotherapy)
other name: ABT-888
other name: PARP-1 inhibitor ABT-888
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jonas De Souza
role: Principal Investigator
affiliation: Alliance for Clinical Trials in Oncology
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Oropharyngeal Neoplasms
mesh term: Paclitaxel
mesh term: Cisplatin
mesh term: Carboplatin
mesh term: Fluorouracil
mesh term: Albumin-Bound Paclitaxel
mesh term: Hydroxyurea
mesh term: Veliparib
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 