NCT06023862 | RECRUITING | Ovarian Neoplasms

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)

Sponsor:

Yonsei University

Information provided by (Responsible Party):

JUNGYUN LEE

Brief Summary:

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 Pegylated liposomal doxorubicin, Doxorubicin, Paclitaxel, and Gemcitabine)

Condition or disease

Ovarian Neoplasms

Endometrial Neoplasms

Uterine Cervical Neoplasms

Vulvar Cancer

Vagina Neoplasm

Clear Cell Carcinoma

Intervention/treatment

Dostarlimab

Bevacizumab

Doxorubicin

Gemcitabine

Paclitaxel

Pegylated liposomal doxorubicin

Phase

PHASE2

Study Type :	INTERVENTIONAL
Estimated Enrollment :	198 participants
Masking :	NONE
Primary Purpose :	TREATMENT
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)
Actual Study Start Date :	2024-01-22
Estimated Primary Completion Date :	2027-08-31
Estimated Study Completion Date :	2029-12-31

Information not available for Arms and Intervention/treatment

Ages Eligible for Study:	18 Years
Sexes Eligible for Study:	FEMALE
Accepts Healthy Volunteers:

Criteria

Inclusion Criteria

1. Female patient is at least 18 years of age,
2. Patient has signed the Informed Consent (ICF) and is able to comply with protocol requirements.
3. Patient with histologically proven confirmed recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, and vulva
* Local review by gynecologic pathologist required
* ≥50% clear cell histology in case of mixed carcinoma
* WT-1 neg (Only in case of ovarian cancer) Note: In the case of including non-ovarian clear cell carcinoma with more than 20 cases, the decision is made through discussion with the SPONSOR.
4. Patient with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
5. Disease progression within 12 months of completing platinum-based chemotherapy
6. 1-5 prior lines of therapies
7. Patient with measurable disease according RECIST 1.1 criteria
8. Availability of Tumor tissue for translational research . - A formalin-fixed paraffin-embedded (FFPE) tumor block(preferred) or at least 20 slides (unstained, freshly cut, serial sections) must be submitted.
9. Patients who consent to fresh tumor biopsies
* Confirmed with at least one lesion with location accessible to safely biopsy per the clinical judgement of the investigator
* Note: If mandatory biopsies cannot be performed as per investigator's clinical judgement, discussion and agreement between investigator and Sponsor are required.
10. Patient has adequate organ function, defined as follows
- 1. Absolute neutrophil count ≥ 1,500 cells/μL
- 2. Platelets ≥ 100,000 cells/μL
- 3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
- 4. Serum creatinine ≤ 1.5× upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault equation for patients with creatinine levels \> 1.5× institutional ULN
- 5. Total bilirubin ≤ 1.5× ULN (≤ 2.0 x ULN in patients with known Gilbert's syndrome) or direct bilirubin ≤ 1× ULN
- 6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN unless liver metastases are present, in which case they must be ≤ 5× ULN
- 7. International normalized ratio or prothrombin time (PT) ≤1.5× ULN and activated partial thromboplastin time ≤1.5× ULN.Participants taking anticoagulants may be included on a stable dose with a therapeutic INR \<3.5. .
- 11. Patient must have a negative serum pregnancy test within 72 hours of the first dose of study medication, unless they are of non-childbearing potential. If a negative result cannot be confirmed by a urine test, a serum pregnancy test is required. Non-childbearing potential is defined as follows
  - 1. Patient is ≥ 45 years of age and has not had menses for \> 1 year.
  - 2. A follicle-stimulating hormone value in the postmenopausal range upon screening evaluation if amenorrhoeic for \< 2 years without a hysterectomy and oophorectomy.
  - 3. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation
    - * Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound, MRI, or CT scan.
    - * Tubal ligation must be confirmed with medical records of the actual procedure.
    - * Information must be captured appropriately within the site's source documents.
    - 12. Patient of childbearing potential must agree to use a highly effective method of contraception with their partners starting from time of consent through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient (Information must be captured appropriately within the site's source documents).
    Exclusion Criteria
    - 1. Patient has had ≥ 6 prior lines of chemotherapy. Surgery of the recurrence is allowed.
    - 2. Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
    - 3. Patient has received prior anticancer therapy (chemotherapy, targeted therapies, hormonal therapy, radiotherapy) within 21 days or \< 5 times the half-life of the most recent therapy prior to Study Day 1, whichever is shorter.
    - Note: Palliative radiation therapy to a small field ≥ 1 week prior to Day 1 of study treatment may be allowed after discussion with the SPONSOR.
    - 4. Patient with contraindication to chemotherapy or immune checkpoint inhibitor treatments or anti-angiogenic inhibitor
    - 5. Patients with uncontrolled hypertension (defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥100 mmHg) based on an average of ≥ 3 BP readings on ≥ 2 sessions.
    - 6. Patients with evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
    - 7. Patients with current abdominal/pelvic fistula
    - 8. Patient has a concomitant malignancy, or patient has a prior non-gynecological malignancy who has been disease-free for \< 3 years or who received any active treatment in the last 3 years for that malignancy. Non-melanoma skin cancer is allowed.
    - 9. Patient has known uncontrolled central nervous system metastases, carcinomatosis meningitis, or both. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of disease progression by imaging \[using the identical imaging modality for each assessment, either MRI or CT scan\] for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not been using steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability.
    - 10. Patient has a known history of human immunodeficiency virus (HIV; HIV ½ antibodies). Participants with known human immunodeficiency virus(HIV) are allowed if they meet all of the following criteria
      - * Cluster of differentiation 4(CD4) ≥350/μL and viral load \<50 copies/mL.
      - * No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months before enrollment.
      - * No history of HIV-associated malignancy for the past 5 years.
      - * Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV started \>4 weeks before study enrollment.
      - 11. Patient with presence of hepatitis B surface antigen or a positive hepatitis C antibody test result at screening or within 3 months before first dose of dostarlimab treatment.
      - * Participants who are hepatitis B surface antigen positive may be enrolled if their HBV-DNA level is below the institutional lower limit.
      - * Participants with chronic hepatitis B virus (HBV) infection who meet the criteria for anti-HBV therapy may be eligible if the participant is on a suppressive antiviral therapy before initiation of cancer therapy.
      - * Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA polymerase chain reaction is obtained. Hepatitis C participants may be eligible if they both have completed curative therapy and have a hepatitis C viral load \
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Singapore,

National University Hospital

Singapore, Singapore,

NCT06023862 | RECRUITING | Ovarian Neoplasms

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)

Sponsor:

Information provided by (Responsible Party):

Brief Summary:

Condition or disease

Intervention/treatment

Phase

Criteria

How to Participate

Locations Map View

Korea, Republic of,

Korea, Republic of,

Korea, Republic of,

Korea, Republic of,

Korea, Republic of,

Korea, Republic of,

Korea, Republic of,

Singapore,

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