<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/NCT03806049</url>
  </required_header>
  <id_info>
    <org_study_id>ENGOT-OV42 / NSGO-AVATAR</org_study_id>
    <nct_id>NCT03806049</nct_id>
  </id_info>
  <brief_title>Trial Comparing Niraparib-bevacizumab-Dostarlimab and Niraparib-bevacizumab to Standard of Care in Recurrent Ovarian Cancer</brief_title>
  <official_title>ENGOT-OV42 / NSGO-AVATAR: A Three-arm Randomized Study to Evaluate the Efficacy of Niraparib-bevacizumab-dostarlimab Triplet Combination Against Niraparib-bevacizumab Doublet Combination and Against Standard of Care Therapy in Women With Relapsed Ovarian Cancer Where Platinum Combination Therapy is an Option.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nordic Society of Gynaecological Oncology - Clinical Trials Unit</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nordic Society of Gynaecological Oncology - Clinical Trials Unit</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      ENGOT-OV42 / NSGO-AVATAR: This three-arm randomized trial is to demonstrate efficacy of&#xD;
      niraparib-bevacizumab-dostarlimab triplet combination against standard of care treatment and&#xD;
      to demonstrate efficacy of niraparib-bevacizumab-dostarlimab triplet combination against&#xD;
      niraparib-bevacizumab doublet combination for patients with platinum-sensitive epithelial&#xD;
      ovarian, fallopian tube, or peritoneal cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter randomized open-label trial to compare two different chemotherapy-free&#xD;
      arms against standard of care treatment in patients with recurrent ovarian cancer with &gt;6&#xD;
      months of chemotherapy-free interval to prior therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of financial support&#xD;
  </why_stopped>
  <start_date type="Anticipated">December 2019</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>randomized, open-label, three arm study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>42 months</time_frame>
    <description>the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival in Sub-Population in months</measure>
    <time_frame>42 months</time_frame>
    <description>the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first for the predefined study subgroups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival 2 in each group according to trial stratification factors</measure>
    <time_frame>58 months</time_frame>
    <description>The time from randomization until date of second objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first for the predefined study subgroups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TFST (Time to First Subsequent Therapy)</measure>
    <time_frame>44 months</time_frame>
    <description>The time from randomization until date of subsequent cancer therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TSST (Time to Second Subsequent Therapy)</measure>
    <time_frame>60 months</time_frame>
    <description>The time from randomization until date of second subsequent cancer therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>72 months</time_frame>
    <description>The time from randomization until date of death due to any cause</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>A: triplet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>chemotherapy-free combination of niraprib + bevacizumab + Dostarlimab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B: Doublet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>chemotherapy-free combination of niraparib + bevacizumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C: standard of care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of care chemotherapy: Carboplatin + paclitaxel</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Niraparib</intervention_name>
    <description>given orally once daily</description>
    <arm_group_label>A: triplet</arm_group_label>
    <arm_group_label>B: Doublet</arm_group_label>
    <other_name>Zejula</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>given as iv infusion every three weeks</description>
    <arm_group_label>A: triplet</arm_group_label>
    <arm_group_label>B: Doublet</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TSR042</intervention_name>
    <description>Given as IV infusion every three weeks</description>
    <arm_group_label>A: triplet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>given as iv infusion every three weeks</description>
    <arm_group_label>C: standard of care</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>given as iv infusion every three weeks</description>
    <arm_group_label>C: standard of care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Recurrent platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer&#xD;
             (platinum sensitivity defined as no recurrence within 6 months of last receipt of&#xD;
             platinum/chemotherapy).&#xD;
&#xD;
          2. High-grade serious or high-grade endometrioid histology or any histology with known&#xD;
             BRCA mutation.&#xD;
&#xD;
          3. Patient consents to perform BRCA test, and PD-L1 expression.&#xD;
&#xD;
          4. Prior line of therapy: Patients must have received platinum-containing therapy for&#xD;
             primary disease.&#xD;
&#xD;
          5. No limits on number of platinum-based therapies.&#xD;
&#xD;
          6. Up to one non-platinum-based line of therapy in recurrent setting is allowed.&#xD;
&#xD;
          7. Patients may have received bevacizumab (or other anti-VEGF therapy) prior to entering&#xD;
             in the trial.&#xD;
&#xD;
          8. Patients may have participated in a PARP inhibitor maintenance trial or have received&#xD;
             maintenance PARP inhibitor therapy are allowed, though it is necessary to unblind&#xD;
             patient in order to correctly stratify. Patients who received a PARP inhibitor as&#xD;
             definitive are not eligible. Patients may have participated in a trial containing&#xD;
             immune-checkpoint inhibitor.&#xD;
&#xD;
          9. Target group: Age 18+&#xD;
&#xD;
         10. Histological confirmed ovarian, fallopian tube or peritoneal cancers&#xD;
&#xD;
         11. Patients must give informed consent&#xD;
&#xD;
         12. Patients may have undergone primary or interval debulking surgery&#xD;
&#xD;
         13. Patients may have received bevacizumab or other anti-angiogenic therapy&#xD;
&#xD;
         14. Patients may have received a PARP inhibitor as first-line maintenance therapy.&#xD;
&#xD;
         15. Patients must have disease that is measurable according to RECIST or assessable&#xD;
             according to the GCIG criteria&#xD;
&#xD;
         16. The patient agrees to complete PROs (QoL questionnaire) during study treatment AND at&#xD;
             one additional time point 8 weeks following progression of disease&#xD;
&#xD;
         17. ECOG performance status 0-2&#xD;
&#xD;
         18. Adequate organ function&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) ≥1,5 x 109/L&#xD;
&#xD;
               2. Platelets &gt;100 x 109/L&#xD;
&#xD;
               3. Hemoglobin ≥ 9g/dl&#xD;
&#xD;
               4. Serum creatinine ≤1.5x upper limit of normal (ULN) or calculated creatinine&#xD;
                  clearance ≥50mL/min using Cockcroft-Gault formula&#xD;
&#xD;
               5. Total bilirubin ≤1.5x ULN&#xD;
&#xD;
               6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x ULN&#xD;
                  unless liver metastases are present, in which case they must be ≤5x ULN.&#xD;
&#xD;
         19. Able to take oral medications&#xD;
&#xD;
         20. Life expectancy of at least 12 weeks&#xD;
&#xD;
         21. Patients must fulfill all inclusions criteria and according to investigator fit to&#xD;
             receive niraparib, bevacizumab and TSR042.&#xD;
&#xD;
         22. Women of childbearing potential must use adequate birth control for the duration of&#xD;
             study participation -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Ovarian sarcomas, small cell carcinoma with neuroendocrine differentiation, non-epithelial&#xD;
        cancers and cancer types not mentioned in the inclusion criteria 2. Concurrent cancer&#xD;
        therapy 3. Concurrent treatment with an investigational agent or participation in another&#xD;
        clinical trial 4. Major injuries or surgery within the past 21 days prior to start of study&#xD;
        treatment with incomplete wound healing and/or planned surgery during the on-treatment&#xD;
        study period 5. Previous malignant disease: patients are not eligible for the study if&#xD;
        diagnosis, detection or treatment of invasive cancer (other than ovarian cancer; with the&#xD;
        exception of basal or squamous cell carcinoma of the skin that was definitively treated)&#xD;
        was detected within 2 years prior to randomization 6. Active infections or other serious&#xD;
        underlying significant medical illness, abnormal laboratory finding or psychiatric&#xD;
        illness/social situation that would, in the Investigator's judgment, makes the patient&#xD;
        inappropriate for this study 7. Gastrointestinal disorders or abnormalities that would&#xD;
        interfere with absorption of the study drug 8. History of bowel obstruction, including&#xD;
        sub-occlusive disease, related to the underlying disease and history of abdominal fistula,&#xD;
        gastrointestinal perforation or intra-abdominal abscess. Evidence of recto-sigmoid&#xD;
        involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of&#xD;
        bowel obstruction 9. Known contraindications to PARP inhibitors, VEGF directed therapy or&#xD;
        immune checkpoint inhibitors 10. Known uncontrolled hypersensitivity to the investigational&#xD;
        drugs 11. History of major thromboembolic event defined as:&#xD;
&#xD;
          -  Uncontrolled pulmonary embolism (PE)&#xD;
&#xD;
          -  Deep venous thrombosis (DVT)&#xD;
&#xD;
          -  Other related conditions, though patients with stable therapeutic anticoagulation for&#xD;
             more than three months prior randomization are eligible for this study. This also&#xD;
             apply to PE &amp; DVT.&#xD;
&#xD;
             12. History of a cerebral vascular accident, transient ischemic attack or subarachnoid&#xD;
             hemorrhage within the past 3 months 13. History of clinically significant hemorrhage&#xD;
             in the past 3 months 14. Uncontrolled and/or symptomatic CNS metastasis or&#xD;
             leptomeningeal carcinomatosis (Dexamethasone/prednisone therapy will be allowed if&#xD;
             administered as stable dose for at least one month prior randomization) 15.&#xD;
             Significant cardiovascular diseases, including uncontrolled hypertension, clinically&#xD;
             relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months&#xD;
             prior to randomization, congestive heart failure &gt; NYHA III, severe peripheral&#xD;
             vascular disease, QT prolongation &gt;470 msec ,clinically significant pericardial&#xD;
             effusion 16. Pregnancy or breastfeeding. Patients with preserved reproductive&#xD;
             capacity, unwilling to use a medically acceptable method of contraception for the&#xD;
             duration of the trial and for 3 months afterwards.&#xD;
&#xD;
             17. Radiographic evidence of cavitation or necrotic tumors with invasion of adjacent&#xD;
             major blood vessels 18. Active or chronic hepatitis C and/or B infection 19.&#xD;
             Persistence of clinically relevant therapy related toxicity from previous chemotherapy&#xD;
             20. Proteinuria as demonstrated by: (a) urine protein: creatinine (UPC) ratio &gt;/= 1.0&#xD;
             at screening OR (b) urine dipstick for proteinuria &gt;/=2+ (patients discovered to have&#xD;
             &gt;/=2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hr urine&#xD;
             collection and must demonstrate &lt;/=1g of protein in24 hours to be eligible 21.&#xD;
             Patients must not have any known history of MDS 22. Patients must not have known&#xD;
             persistent (&gt; 4 weeks) ≥ Grade 2 hematological toxicity from prior cancer therapy 23.&#xD;
             Patients must not have known ≥ Grade 3 thrombocytopenia or anemia with the last&#xD;
             chemotherapy regimen.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MANSOOR RAZA R MIRZA</last_name>
    <role>Study Chair</role>
    <affiliation>NSGO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NSGO</name>
      <address>
        <city>Copenhagen</city>
        <state>Sjaelland</state>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <state>Sjaelland</state>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>København Ø</city>
        <state>Sjaelland</state>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aalborg University Hospital</name>
      <address>
        <city>Aalborg</city>
        <zip>9000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tampere University Hospital</name>
      <address>
        <city>Tampere</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haukeland University Hospital</name>
      <address>
        <city>Bergen</city>
        <state>Haukeland</state>
        <zip>5021</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norwegian Radium Hospital</name>
      <address>
        <city>Oslo</city>
        <zip>0310</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Norwegian Radium Hospital</name>
      <address>
        <city>Oslo</city>
        <zip>0310</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Finland</country>
    <country>Norway</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>January 13, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>July 9, 2021</last_update_submitted>
  <last_update_submitted_qc>July 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>chemotherapy-free regimen</keyword>
  <keyword>niraparib</keyword>
  <keyword>bevacizumab</keyword>
  <keyword>dostarlimab</keyword>
  <keyword>recurrent ovarian cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Niraparib</mesh_term>
    <mesh_term>Dostarlimab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>All individual participant data will be anonymized</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03806049
org study id: ENGOT-OV42 / NSGO-AVATAR
nct id: NCT03806049
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
ENGOT-OV42 / NSGO-AVATAR: This three-arm randomized trial is to demonstrate efficacy of
      niraparib-bevacizumab-dostarlimab triplet combination against standard of care treatment and
      to demonstrate efficacy of niraparib-bevacizumab-dostarlimab triplet combination against
      niraparib-bevacizumab doublet combination for patients with platinum-sensitive epithelial
      ovarian, fallopian tube, or peritoneal cancer
This is a multicenter randomized open-label trial to compare two different chemotherapy-free
      arms against standard of care treatment in patients with recurrent ovarian cancer with >6
      months of chemotherapy-free interval to prior therapy.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: randomized, open-label, three arm study
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free Survival
time frame: 42 months
description: the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first.
measure: Progression Free Survival in Sub-Population in months
time frame: 42 months
description: the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first for the predefined study subgroups.
measure: Progression Free Survival 2 in each group according to trial stratification factors
time frame: 58 months
description: The time from randomization until date of second objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first for the predefined study subgroups
measure: TFST (Time to First Subsequent Therapy)
time frame: 44 months
description: The time from randomization until date of subsequent cancer therapy
measure: TSST (Time to Second Subsequent Therapy)
time frame: 60 months
description: The time from randomization until date of second subsequent cancer therapy
measure: Overall survival (OS)
time frame: 72 months
description: The time from randomization until date of death due to any cause
arm group label: A: triplet
arm group type: Experimental
description: chemotherapy-free combination of niraprib + bevacizumab + Dostarlimab
arm group label: B: Doublet
arm group type: Experimental
description: chemotherapy-free combination of niraparib + bevacizumab
arm group label: C: standard of care
arm group type: Active Comparator
description: Standard of care chemotherapy: Carboplatin + paclitaxel
intervention type: Drug
intervention name: Niraparib
description: given orally once daily
arm group label: A: triplet
arm group label: B: Doublet
other name: Zejula
intervention type: Drug
intervention name: Bevacizumab
description: given as iv infusion every three weeks
arm group label: A: triplet
arm group label: B: Doublet
other name: Avastin
intervention type: Drug
intervention name: TSR042
description: Given as IV infusion every three weeks
arm group label: A: triplet
intervention type: Drug
intervention name: Carboplatin
description: given as iv infusion every three weeks
arm group label: C: standard of care
intervention type: Drug
intervention name: Paclitaxel
description: given as iv infusion every three weeks
arm group label: C: standard of care
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: MANSOOR RAZA R MIRZA
role: Study Chair
affiliation: NSGO
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Denmark
country: Finland
country: Norway
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Paclitaxel
mesh term: Bevacizumab
mesh term: Carboplatin
mesh term: Niraparib
mesh term: Dostarlimab
sharing ipd: No
ipd description: All individual participant data will be anonymized