xml: <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/NCT06023862</url>
    </required_header>
    <id_info>
      <org_study_id>4-2023-0794</org_study_id>
      <nct_id>NCT06023862</nct_id>
    </id_info>
    <brief_title>A Three-arm Randomized Phase II Study of Dostarlimab Alone or With Bevacizumab Versus Nonplatinum Chemotherapy in Recurrent Gynecological Clear Cell Carcinoma: DOVE (APGOT-ov7/ ENGOT-ov80 Study)</brief_title>
    <acronym>DOVE</acronym>
    <official_title>A Three-arm Randomized Phase II Study of Dostarlimab Alone or With Bevacizumab Versus Nonplatinum Chemotherapy in Recurrent Gynecological Clear Cell Carcinoma: DOVE (APGOT-OV07/ ENGOT-OV80 Study)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Yonsei University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Yonsei University</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>
        Multicenter, randomized, open-label, phase II clinical study comparing Dostarlimab +/-&#xD;
        Bevacizumab with standard chemotherapy in patients with gynecological clear cell carcinoma.&#xD;
  &#xD;
        198 subjects will be enrolled in this study and will be assigned to three groups in a 1:1:1&#xD;
        ratio.&#xD;
  &#xD;
          1. Group A: Dostarlimab monotherapy&#xD;
  &#xD;
               -  First 3 cycles: Dostalimab 500mg every 3 weeks, IV&#xD;
  &#xD;
               -  4 cycles ~ up to 24 months: Dostalimab 1000mg every 6 weeks, IV&#xD;
  &#xD;
          2. Group B: Dostarlimab + Bevacizumab combination therapy&#xD;
  &#xD;
               -  First 3 cycles: Dostalimab 500mg every 3 weeks, IV&#xD;
  &#xD;
               -  4 cycles ~ up to 24 months: Dostalimab 1000mg every 6 weeks, IV&#xD;
  &#xD;
               -  Bevacizumab administered IV at 15 mg/kg every 3 weeks until disease progression or&#xD;
                  unacceptable toxicity&#xD;
  &#xD;
          3. Group C: General chemotherapy (one of doxorubicin, paclitaxel, and gemcitabine)&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 25, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2029</completion_date>
    <primary_completion_date type="Anticipated">August 31, 2027</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Progression Free Survival</measure>
      <time_frame>Up to approximately 48 months</time_frame>
      <description>The time from the date of randomization until first documentation of disease progression, as determined by investigator assessment based on RECIST 1.1, or death due to any cause, whichever occurs first.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate</measure>
      <time_frame>Up to approximately 48 months</time_frame>
      <description>the proportion of patients who have best overall response of either complete response (CR) or partial response (PR), as investigator assessment based on RECIST 1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate</measure>
      <time_frame>Up to approximately 48 months</time_frame>
      <description>the proportion of patients who have best overall response of CR, PR, or stable disease (SD) by investigator assessment per RECIST 1.1 . SD must be achieved at ≥ 7 weeks after randomization to be considered best overall response.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical benefit rate</measure>
      <time_frame>Up to approximately 48 months</time_frame>
      <description>the proportion of patients who have best overall response of CR, PR, or stable disease (SD) by investigator assessment per RECIST 1.1 . (duration of SD ≥ 23 weeks after randomization)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression Free Survival 2</measure>
      <time_frame>Up to approximately 72 months</time_frame>
      <description>the time from initial randomization to the second objective disease progression (ie, after the first subsequent therapy) or death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>Up to approximately 72 months</time_frame>
      <description>the time from the date of randomization until death due to any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response Rate</measure>
      <time_frame>Up to approximately 48 months</time_frame>
      <description>Measured from the time of initial response until documented tumor progression.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]</measure>
      <time_frame>Up to approximately 72 months</time_frame>
      <description>Assessed by CTCAE v5.0 (by investigators).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to first and second Subsequent Treatment</measure>
      <time_frame>Up to approximately 72 months</time_frame>
      <description>the time from the date of randomization to date of the first and second subsequent anticancer therapy or death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Response rate of subsequent therapies</measure>
      <time_frame>Up to approximately 72 months</time_frame>
      <description>the proportion of patients who have best overall response of either complete response (CR) or partial response (PR), as investigator assessment based on RECIST 1.1</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Disease-related or Treatment-related Biomarkers</measure>
      <time_frame>At the end of study, Up to approximately 72 months</time_frame>
      <description>Translational research including NGS as well as MMRd, MSI-H, PD1/L1, TMB, Immune signature, and Tie-2.</description>
    </other_outcome>
    <other_outcome>
      <measure>Comparison of RECIST1.1 and i-RECIST assessment</measure>
      <time_frame>Throughout duration of study, Up to 48 months</time_frame>
      <description>By comparing RECIST 1.1 and iRECIST, evaluate the accuracy of iRECIST for assessing the therapeutic efficacy of ICIs.</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">198</enrollment>
    <condition>Ovarian Neoplasms</condition>
    <condition>Endometrial Neoplasms</condition>
    <condition>Uterine Cervical Neoplasms</condition>
    <condition>Vulvar Cancer</condition>
    <condition>Vagina Neoplasm</condition>
    <condition>Clear Cell Carcinoma</condition>
    <arm_group>
      <arm_group_label>Group A</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Dostarlimab monotherapy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group B</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Dostarlimab + Bevacizumab combination therapy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group C</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>General chemotherapy (one of doxorubicin, paclitaxel, and gemcitabine)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dostarlimab</intervention_name>
      <description>Intravenous (IV) infusion</description>
      <arm_group_label>Group A</arm_group_label>
      <arm_group_label>Group B</arm_group_label>
      <other_name>Jemperli</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Bevacizumab</intervention_name>
      <description>Intravenous (IV) infusion</description>
      <arm_group_label>Group B</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Doxorubicin</intervention_name>
      <description>Intravenous (IV) infusion</description>
      <arm_group_label>Group C</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Gemcitabine</intervention_name>
      <description>Intravenous (IV) infusion</description>
      <arm_group_label>Group C</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Paclitaxel</intervention_name>
      <description>Intravenous (IV) infusion</description>
      <arm_group_label>Group C</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Female patient is at least 18 years of age,&#xD;
  &#xD;
            2. Patient has signed the Informed Consent (ICF) and is able to comply with protocol&#xD;
               requirements.&#xD;
  &#xD;
            3. Patient with histologically proven confirmed recurrent or persistent clear cell&#xD;
               carcinoma of the ovary, endometrium, cervix, vagina, and vulva - Local review by&#xD;
               gynecologic pathologist required&#xD;
  &#xD;
                 -  ≥50% clear cell histology in case of mixed carcinoma&#xD;
  &#xD;
                 -  WT-1 neg (Only in case of ovarian cancer) Note: In the case of including&#xD;
                    non-ovarian clear cell carcinoma with more than 20 cases, the decision is made&#xD;
                    through discussion with the SPONSOR.&#xD;
  &#xD;
            4. Patient with an Eastern Cooperative Oncology Group (ECOG) performance status score of&#xD;
               0 or 1.&#xD;
  &#xD;
            5. Disease progression within 12 months of completing platinum-based chemotherapy&#xD;
  &#xD;
            6. 1-5 prior lines of therapies&#xD;
  &#xD;
            7. Patient with measurable disease according RECIST 1.1 criteria&#xD;
  &#xD;
            8. Availability of Tumor tissue for for translational research - A formalin-fixed&#xD;
               paraffin-embedded (FFPE) tumor block(preferred) or at least 20 slides (unstained,&#xD;
               freshly cut, serial sections) must be submitted.&#xD;
  &#xD;
            9. Patients who consent to fresh tumor biopsies - Confirmed with at least one lesion with&#xD;
               location accessible to safely biopsy per the clinical judgement of the investigator&#xD;
  &#xD;
               - Note: If mandatory biopsies cannot be performed as per investigator's clinical&#xD;
               judgement, discussion and agreement between investigator and Sponsor are required.&#xD;
  &#xD;
           10. Patient has adequate organ function, defined as follows (Specimens must be collected&#xD;
               within 7 days prior to randomization) :&#xD;
  &#xD;
               a) Absolute neutrophil count ≥ 1,500 cells/μL b) Platelets ≥ 100,000 cells/μL c)&#xD;
               Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L d) Serum creatinine ≤ 1.5× upper limit of normal&#xD;
               (ULN) or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault&#xD;
               equation for patients with creatinine levels &gt; 1.5× institutional ULN e) Total&#xD;
               bilirubin ≤ 1.5× ULN (≤ 2.0 x ULN in patients with known Gilbert's syndrome) or direct&#xD;
               bilirubin ≤ 1× ULN f) Aspartate aminotransferase (AST) and alanine aminotransferase&#xD;
               (ALT) ≤ 2.5× ULN unless liver metastases are present, in which case they must be ≤ 5×&#xD;
               ULN&#xD;
  &#xD;
           11. International normalized ratio or prothrombin time (PT) ≤1.5× ULN and activated&#xD;
               partial thromboplastin time ≤1.5× ULN. Participants taking anticoagulants may be&#xD;
               included on a stable dose with a therapeutic INR &lt;3.5 .&#xD;
  &#xD;
           12. Patient must have a negative serum pregnancy test within 72 hours of the first dose of&#xD;
               study medication, unless they are of non-childbearing potential. Non-childbearing&#xD;
               potential is defined as follows:&#xD;
  &#xD;
                 1. Patient is ≥ 45 years of age and has not had menses for &gt; 1 year.&#xD;
  &#xD;
                 2. A follicle-stimulating hormone value in the postmenopausal range upon screening&#xD;
                    evaluation if amenorrhoeic for &lt; 2 years without a hysterectomy and oophorectomy.&#xD;
  &#xD;
                 3. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation:&#xD;
  &#xD;
                    - Documented hysterectomy or oophorectomy must be confirmed with medical records&#xD;
                    of the actual procedure or confirmed by an ultrasound, MRI, or CT scan.&#xD;
  &#xD;
                    - Tubal ligation must be confirmed with medical records of the actual procedure.&#xD;
  &#xD;
                    - Information must be captured appropriately within the site's source documents.&#xD;
  &#xD;
           13. Patient of childbearing potential must agree to use a highly effective method of&#xD;
               contraception with their partners starting from time of consent through 180 days after&#xD;
               the last dose of study treatment. Note: Abstinence is acceptable if this is the&#xD;
               established and preferred contraception for the patient (Information must be captured&#xD;
               appropriately within the site's source documents).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patient has had ≥ 6 prior lines of chemotherapy. Surgery of the recurrence is allowed.&#xD;
  &#xD;
            2. Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.&#xD;
  &#xD;
            3. Patient has received prior anticancer therapy (chemotherapy, targeted therapies,&#xD;
               hormonal therapy, radiotherapy) within 21 days or &lt; 5 times the half-life of the most&#xD;
               recent therapy prior to Study Day 1, whichever is shorter.&#xD;
  &#xD;
               Note: Palliative radiation therapy to a small field ≥ 1 week prior to Day 1 of study&#xD;
               treatment may be allowed after discussion with the Sponsor.&#xD;
  &#xD;
            4. Patient with contraindication to chemotherapy or immune checkpoint inhibitor&#xD;
               treatments or antiangiogenic inhibitor&#xD;
  &#xD;
            5. Patients with uncontrolled hypertension (defined as systolic blood pressure ≥ 160 mmHg&#xD;
               and/or diastolic blood pressure ≥100 mmHg) based on an average of ≥ 3 BP readings on ≥&#xD;
               2 sessions.&#xD;
  &#xD;
            6. Patients with evidence of bleeding diathesis or significant coagulopathy (in the&#xD;
               absence of therapeutic anticoagulation)&#xD;
  &#xD;
            7. Patients with current abdominal/pelvic fistula&#xD;
  &#xD;
            8. Patient has a concomitant malignancy, or patient has a prior non-gynecological&#xD;
               malignancy who has been disease-free for &lt; 3 years or who received any active&#xD;
               treatment in the last 3 years for that malignancy. Non-melanoma skin cancer is&#xD;
               allowed.&#xD;
  &#xD;
            9. Patient has known uncontrolled central nervous system metastases, carcinomatosis&#xD;
               meningitis, or both. Note: Patients with previously treated brain metastases may&#xD;
               participate provided they are stable (without evidence of disease progression by&#xD;
               imaging [using the identical imaging modality for each assessment, either MRI or CT&#xD;
               scan] for at least 4 weeks prior to the first dose of study treatment and any&#xD;
               neurologic symptoms have returned to baseline), have no evidence of new or enlarging&#xD;
               brain metastases, and have not been using steroids for at least 7 days prior to study&#xD;
               treatment. Carcinomatous meningitis precludes a patient from study participation&#xD;
               regardless of clinical stability.&#xD;
  &#xD;
           10. Patient has a known history of human immunodeficiency virus (HIV; HIV ½ antibodies).&#xD;
               Participants with known human immunodeficiency virus(HIV) are allowed if they meet all&#xD;
               of the following criteria:&#xD;
  &#xD;
               - Cluster of differentiation 4(CD4) ≥350/μL and viral load &lt;50 copies/mL.&#xD;
  &#xD;
               - No history of acquired immunodeficiency syndrome-defining opportunistic infections&#xD;
               within 12 months before enrollment.&#xD;
  &#xD;
                 -  No history of HIV-associated malignancy for the past 5 years.&#xD;
  &#xD;
                 -  Concurrent antiretroviral therapy as per the most current National Institutes of&#xD;
                    Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and&#xD;
                    Adolescents with HIV started &gt;4 weeks before study enrollment.&#xD;
  &#xD;
           11. Patient with presence of hepatitis B surface antigen or a positive hepatitis C&#xD;
               antibody test result at screening or within 3 months before first dose of dostarlimab&#xD;
               treatment. participants with presence of hepatitis B core antibody should also be&#xD;
               excluded.&#xD;
  &#xD;
                 -  Participants with chronic hepatitis B virus (HBV) infection who meet the criteria&#xD;
                    for anti-HBV therapy may be eligible if the participant is on a suppressive&#xD;
                    antiviral therapy before initiation of cancer therapy.&#xD;
  &#xD;
                 -  Participants with positive hepatitis C antibody due to prior resolved disease can&#xD;
                    be enrolled only if a confirmatory negative hepatitis C RNA polymerase chain&#xD;
                    reaction is obtained. Hepatitis C participants may be eligible if they both have&#xD;
                    completed curative therapy and have a hepatitis C viral load &lt;!-- Not Allowed Tag&#xD;
                    Filtered --&gt;&lt;quantifiable limit. 12. Patient has an active autoimmune disease&#xD;
                    that required systemic treatment in the past 2 years. Replacement therapy is not&#xD;
                    considered a form of (eg, thyroid hormone or insulin). 13. diagnosis&#xD;
                    immunodeficiency receiving steroid any other immunosuppressive within 7 days&#xD;
                    prior to first dose study treatment. Patients who have received acute and&gt;/or&#xD;
                    low-dose systemic immunosuppressive medications (e.g,, a one-time dose of&#xD;
                    dexamethasone for nausea or chronic use of ≤ 10 mg/day of prednisone or dose&#xD;
                    equivalent corticosteroid) may be enrolled in the study after discussion with and&#xD;
                    approval by the Sponsor. The use of inhaled corticosteroids and&#xD;
                    mineralocorticoids (e.g., fludrocortisone) is allowed.&#xD;
  &#xD;
          14. Patient has not recovered (ie, to Grade ≤ 1) from previous anti-cancer therapy-induced&#xD;
          adverse events (AEs).&#xD;
  &#xD;
          Note: Patients with Grade ≤ 2 neuropathy, Grade ≤ 2 alopecia, or Grade ≤ 2 fatigue are an&#xD;
          exception to this criterion and may qualify for the study.&#xD;
  &#xD;
          15. Patient has not recovered adequately from AEs or complications from any major surgery&#xD;
          prior to starting therapy. Major surgical procedures, other than for diagnosis, within 4&#xD;
          weeks prior to initiation of study treatment 16. Patient has a known hypersensitivity to&#xD;
          bevacizumab or dostarlimab components or excipients.&#xD;
  &#xD;
          17. Patient is currently participating and receiving study treatment or has participated in&#xD;
          a study of an investigational agent and received study treatment or used an investigational&#xD;
          device within 4 weeks of the first dose of treatment.&#xD;
  &#xD;
          18. Patient is considered a poor medical condition due to a serious, uncontrolled medical&#xD;
          disorder, non-malignant systemic disease, or active infection requiring systemic therapy.&#xD;
          Specific examples include, but are not limited to, active, non-infectious pneumonitis;&#xD;
          uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction;&#xD;
          uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava&#xD;
          syndrome; or any psychiatric or substance abuse disorders that would interfere with&#xD;
          cooperation with the requirements of the study (including obtaining informed consent).&#xD;
  &#xD;
          19. Patients with known history of non-infectious pneumonitis that required steroids or has&#xD;
          current pneumonitis 20. Use of any of the following immunomodulatory agents within 28 days&#xD;
          prior to the first dose of study drug:&#xD;
  &#xD;
            -  Interferons&#xD;
  &#xD;
            -  Interleukins&#xD;
  &#xD;
            -  Live vaccine Note: Examples of live vaccines include, but are not limited to, the&#xD;
               following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and&#xD;
               typhoid vaccine. mRNA and adenoviral-based COVID-19 vaccines are considered non-live&#xD;
               and are not exclusionary. Seasonal influenza vaccines for injection are generally&#xD;
               killed virus vaccines and are allowed as other killed vaccines, if done at least 2&#xD;
               weeks prior the first dose of study drug; however, intranasal influenza vaccines (eg,&#xD;
               FluMist®) are live attenuated vaccines and are not allowed.&#xD;
  &#xD;
               21. Patient who are pregnant or lactating, or plan to become pregnant or lactate&#xD;
               during the expected duration of the study, from screening through 180 days after the&#xD;
               last dose of study drug.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>JUNGYUN LEE, Ph.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Severance Hospital, Yonsei University Health System</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>JUNGYUN LEE, Ph.D.</last_name>
      <phone>82)2-2228-2237</phone>
      <email>JUNGYUNLEE@yuhs.ac</email>
    </overall_contact>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>September 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>September 3, 2023</last_update_submitted>
    <last_update_submitted_qc>September 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Yonsei University</investigator_affiliation>
      <investigator_full_name>JUNGYUN LEE</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma</mesh_term>
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Vulvar Neoplasms</mesh_term>
      <mesh_term>Ovarian Neoplasms</mesh_term>
      <mesh_term>Uterine Cervical Neoplasms</mesh_term>
      <mesh_term>Endometrial Neoplasms</mesh_term>
      <mesh_term>Adenomyoepithelioma</mesh_term>
      <mesh_term>Adenocarcinoma, Clear Cell</mesh_term>
      <mesh_term>Vaginal 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>Bevacizumab</mesh_term>
      <mesh_term>Gemcitabine</mesh_term>
      <mesh_term>Doxorubicin</mesh_term>
      <mesh_term>Dostarlimab</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06023862
  org study id: 4-2023-0794
  nct id: NCT06023862
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Multicenter, randomized, open-label, phase II clinical study comparing Dostarlimab +/-
        Bevacizumab with standard chemotherapy in patients with gynecological clear cell carcinoma.
  
        198 subjects will be enrolled in this study and will be assigned to three groups in a 1:1:1
        ratio.
  
          1. Group A: Dostarlimab monotherapy
  
               -  First 3 cycles: Dostalimab 500mg every 3 weeks, IV
  
               -  4 cycles ~ up to 24 months: Dostalimab 1000mg every 6 weeks, IV
  
          2. Group B: Dostarlimab + Bevacizumab combination therapy
  
               -  First 3 cycles: Dostalimab 500mg every 3 weeks, IV
  
               -  4 cycles ~ up to 24 months: Dostalimab 1000mg every 6 weeks, IV
  
               -  Bevacizumab administered IV at 15 mg/kg every 3 weeks until disease progression or
                  unacceptable toxicity
  
          3. Group C: General chemotherapy (one of doxorubicin, paclitaxel, and gemcitabine)
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression Free Survival
  time frame: Up to approximately 48 months
  description: The time from the date of randomization until first documentation of disease progression, as determined by investigator assessment based on RECIST 1.1, or death due to any cause, whichever occurs first.
  measure: Objective Response Rate
  time frame: Up to approximately 48 months
  description: the proportion of patients who have best overall response of either complete response (CR) or partial response (PR), as investigator assessment based on RECIST 1.1
  measure: Disease control rate
  time frame: Up to approximately 48 months
  description: the proportion of patients who have best overall response of CR, PR, or stable disease (SD) by investigator assessment per RECIST 1.1 . SD must be achieved at ≥ 7 weeks after randomization to be considered best overall response.
  measure: Clinical benefit rate
  time frame: Up to approximately 48 months
  description: the proportion of patients who have best overall response of CR, PR, or stable disease (SD) by investigator assessment per RECIST 1.1 . (duration of SD ≥ 23 weeks after randomization)
  measure: Progression Free Survival 2
  time frame: Up to approximately 72 months
  description: the time from initial randomization to the second objective disease progression (ie, after the first subsequent therapy) or death.
  measure: Overall survival
  time frame: Up to approximately 72 months
  description: the time from the date of randomization until death due to any cause
  measure: Duration of Response Rate
  time frame: Up to approximately 48 months
  description: Measured from the time of initial response until documented tumor progression.
  measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
  time frame: Up to approximately 72 months
  description: Assessed by CTCAE v5.0 (by investigators).
  measure: Time to first and second Subsequent Treatment
  time frame: Up to approximately 72 months
  description: the time from the date of randomization to date of the first and second subsequent anticancer therapy or death.
  measure: Response rate of subsequent therapies
  time frame: Up to approximately 72 months
  description: the proportion of patients who have best overall response of either complete response (CR) or partial response (PR), as investigator assessment based on RECIST 1.1
  measure: Disease-related or Treatment-related Biomarkers
  time frame: At the end of study, Up to approximately 72 months
  description: Translational research including NGS as well as MMRd, MSI-H, PD1/L1, TMB, Immune signature, and Tie-2.
  measure: Comparison of RECIST1.1 and i-RECIST assessment
  time frame: Throughout duration of study, Up to 48 months
  description: By comparing RECIST 1.1 and iRECIST, evaluate the accuracy of iRECIST for assessing the therapeutic efficacy of ICIs.
  arm group label: Group A
  arm group type: Experimental
  description: Dostarlimab monotherapy
  arm group label: Group B
  arm group type: Experimental
  description: Dostarlimab + Bevacizumab combination therapy
  arm group label: Group C
  arm group type: Active Comparator
  description: General chemotherapy (one of doxorubicin, paclitaxel, and gemcitabine)
  intervention type: Drug
  intervention name: Dostarlimab
  description: Intravenous (IV) infusion
  arm group label: Group A
  arm group label: Group B
  other name: Jemperli
  intervention type: Drug
  intervention name: Bevacizumab
  description: Intravenous (IV) infusion
  arm group label: Group B
  intervention type: Drug
  intervention name: Doxorubicin
  description: Intravenous (IV) infusion
  arm group label: Group C
  intervention type: Drug
  intervention name: Gemcitabine
  description: Intravenous (IV) infusion
  arm group label: Group C
  intervention type: Drug
  intervention name: Paclitaxel
  description: Intravenous (IV) infusion
  arm group label: Group C
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: JUNGYUN LEE, Ph.D.
  role: Principal Investigator
  affiliation: Severance Hospital, Yonsei University Health System
  last name: JUNGYUN LEE, Ph.D.
  phone: 82)2-2228-2237
  email: JUNGYUNLEE@yuhs.ac
  responsible party type: Principal Investigator
  investigator affiliation: Yonsei University
  investigator full name: JUNGYUN LEE
  investigator title: Professor
  mesh term: Carcinoma
  mesh term: Neoplasms
  mesh term: Vulvar Neoplasms
  mesh term: Ovarian Neoplasms
  mesh term: Uterine Cervical Neoplasms
  mesh term: Endometrial Neoplasms
  mesh term: Adenomyoepithelioma
  mesh term: Adenocarcinoma, Clear Cell
  mesh term: Vaginal Neoplasms
  mesh term: Paclitaxel
  mesh term: Bevacizumab
  mesh term: Gemcitabine
  mesh term: Doxorubicin
  mesh term: Dostarlimab