A three-arm randomized phase II study of Dostarlimab alone or with Bevacizumab versus nonplatinum chemotherapy in recurrent gynecological clear cell carcinoma (DOVE)
Recruiting
- Conditions
- Ovarian clear cell carcinoma
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Female
- Target Recruitment
- 40
Inclusion Criteria
- Female patient is at least 18 years of age,
- Patient has signed the Informed Consent (ICF) and is able to comply with protocol requirements.
- Patient with histologically proven confirmed recurrent or persistent clear cell carcinoma of the ovary
- Local review by gynecologic pathologist required
-
=50 % clear cell histology in case of mixed carcinoma
- WT-1 neg
- Patient with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Disease progression within 12 months of completing platinum-based chemotherapy
- 1-5 prior lines of therapies
7)Patient with measurable disease according RECIST 1.1 criteria - Availability of Tumor tissue for translational research.
- Patients who consent to fresh tumor biopsies
- Patient has adequate organ function, defined as follows:
a. Absolute neutrophil count >= 1500 cells/uL
b. Platelets >= 100000 cells/uL
c. Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
d. Serum creatinine <= 1.5x upper limit of normal (ULN)
or calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault equation for patients with creatinine levels > 1.5x institutional ULN e. Total bilirubin <= 1.5x ULN (<= 2.0 x ULN in patients with known Gilbert's syndrome) or direct bilirubin <= 1x ULN f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5x ULN unless liver metastases are present, in which case they must be <= 5x ULN g. International normalized ratio (INR) or prothrombin time (PT) <=1.5x ULN and activated partial thromboplastin time <= 1.5x ULN. Participants taking anticoagulants may be included on a stable dose with a therapeutic INR < 3.5. - 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.
- 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.
Exclusion Criteria
- Patient has had >= 6 prior lines of chemotherapy. Surgery of the recurrence is allowed.
- Patient has received prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent.
- 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.
- Patient with contraindication to chemotherapy or immune checkpoint inhibitor treatments or anti-angiogenic inhibitor
- 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.
- Patients with evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- Patients with current abdominal/pelvic fistula
- 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.
- Patient has known uncontrolled central nervous system metastases, carcinomatosis meningitis, or both.
- Patient has a known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
- 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.
- Patient has an active autoimmune disease that has required systemic treatment in the past 2 years.
- Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Patient has not recovered (to Grade <= 1) from previous anti-cancer therapy-induced adverse events (AEs).
- Patient has not recovered adequately from AEs or complications from any major surgery prior to starting therapy.
- Patient has a known hypersensitivity to bevacizumab or dostarlimab components or excipients.
- Patient is currently participating and receiving study treatment or has participated in a study of an investigational agent and received study treatment or used an investigational device within 4 weeks of the first dose of treatment.
- Patient is considered a poor medical condition due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active infection requiring systemic therapy.
- Patients with known history of non-infectious pneumonitis that required steroids or has current pneumonitis
- Use of any of the immunomodulatory agents within 28 days prior to the first dose of study drug
- Patient who are pregnant or lactating, or plan to become pregnant or lactate during the expected duration of the study, from screening through 180 days after the last dose of study drug.
Study & Design
- Study Type
- Interventional
- Study Design
- parallel assignment
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Defined as 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.
- Secondary Outcome Measures
Name Time Method Progression Free Survival 2(PFS2) Defined by the time from initial randomization to the second objective disease progression (i.e. after the first subsequent therapy) or death.
Objective Response Rate (ORR) Defined as 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
Disease control rate (DCR) >= 7 weeks after randomization Defined as 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.
Clinical benefit rate (CBR) >= 23 weeks after randomization Defined as 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)
Duration of Response Rate (DoR) Measured from the time of initial response until documented tumor progression.
Safety and tolerability Assessed by CTCAE v 5.0 (by investigators).
Time to first and second Subsequent Treatment Defined as the time from the date of randomization to date of the first and second subsequent anticancer therapy or death.
Overall survival (OS) Defined as the time from the date of randomization until death due to any cause