A multicentric randomized phase II/III evaluating TSR-042 (anti-PD-1 mAb) in combination with Niraparib (parpi) versus Niraparib alone compared to chemotherapy in the treatment of metastatic or recurrent endometrial or ovarian carcinosarcoma after at least one line of chemotherapy - ROCSA
- Conditions
- metastatic or recurrent endometrial or ovarian carcinosarcomaMedDRA version: 21.1Level: PTClassification code 10057529Term: Ovarian cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10014734Term: Endometrial cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10014736Term: Endometrial cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002662-12-FR
- Lead Sponsor
- ARCAGY-GINECO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 196
1.Progressive or recurrent uterine or ovarian carcinosarcoma (Malignant Mixed Mullerian Tumor-MMMT).
2.The primary diagnosis must be histologically confirmed and central pathological review of the initial tumor or biopsy at relapse will be done.
3.Mandatory tumor sample: Availability of tumor sample from a recently (not older than 3 months) obtained archival FFPE tumor tissue block or agreement for having a new tumor biopsy if lesion amenable.
4.Progressive disease as defined by RECIST 1.1. within 12 months from last chemotherapy cycle.
5.Failure after =1 prior platinum containing regimen, which may have been given in the adjuvant setting.
6.Patient must have had 1 prior chemotherapeutic regimen for management of carcinosarcoma that may have included chemotherapy, chemotherapy and radio-chemotherapy, and/or consolidation/maintenance therapy.
7.Patient must be free of active infection requiring antibiotics.
8.Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to beginning protocol chemotherapy; continuation of hormone replacement therapy is permitted.
9.Patient must have ECOG Performance Status <2.
10.Life expectancy of > 2 months.
11.Adequate bone marrow function:
Platelet count greater than or equal to 100,000/mm3
Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3
Hemoglobin > 9g/dL
12.Adequate hepatic and renal function:
Total bilirubin =1.5x Upper Limit of Normal (ULN) unless liver metastases are present, in which case they must be =3x ULN (=2.0 in patients with known Gilberts syndrome OR direct bilirubin = 1 x ULN)
Serum creatinine =1.5x upper limit of normal (ULN) or calculated creatinine clearance = 60 mL/min using Cockcroft-Gault equation
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5x ULN unless liver metastases are present, in which case they must be =5x ULN
Alkaline phosphatase < 2.5 times ULN
Serum albumin > 3 g/dL
13.International normalized ratio (INR) or prothrombin time (PT) =1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) =1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
14.Patient must have normal BP or adequately treated and controlled hypertension (systolic BP=140 mmHg and/or diastolic BP =90 mmHg)
15.Patient receiving corticosteroids may continue as long as their dose is stable and =10mg/day (prednisone equivalent) for at least 4 weeks prior to initiating protocol therapy.
16.Patient must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
17.Left ventricular ejection fraction (LVEF) > Lower Limit of Normal (LLN) as assessed by either multigated acquisition (MUGA) scan or echocardiogram (ECHO), for patients planned to receive Anthracycline based therapy.
18.Patient has a negative urine or serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential.
-Non-childbearing potential is defined as follows:
-=45 years of age and has not had menses for >1 year
-Patients who have been amenorrhoeic for <2 years without histor
1.Not enrolled in any interventional clinical trial (except to biological trials that must be validated by the sponsor)
2.Prior treatment with niraparib or other PARPi therapy or PD1/PDL-1 inhibitors.
3.Patient has had investigational therapy, immunotherapy, chemotherapy or biological therapy administered within 4 weeks or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to randomization.
Patient has had radiotherapy within 4 weeks prior to randomization.
4.Patients must not have had major surgery = 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
5.Previous treatment with the chemotherapy regimen selected as the control arm by the investigator.
Prior therapy with paclitaxel given on a three-weekly regimen is permitted for patients receiving weekly Paclitaxel.
Prior treatment with weekly paclitaxel is permitted where this has been used as part of first line therapy and it is greater than 6 months since the last dose of weekly paclitaxel.
Prior weekly paclitaxel for relapsed disease is not permitted.
6.Patient who have received more than 3 prior cytotoxic chemotherapies for management of uterine or ovarian carcinosarcoma.
7.Patient with persistent, clinically significant > Grade 1 toxicity.
8.Patient has clinically significant cardiovascular disease (eg, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, uncontrolled cardiac arrhythmia or unstable angina < 6 months to enrollment, NYHA grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident within 6 months)
9.Patient with any other severe concurrent disease, which may increase the risk associated with study participation or study drug administration and, in the judgment of the investigator, would make the patient inappropriate for entry into this study, including significant neurologic, psychiatric, infectious, hepatic, renal, or gastrointestinal diseases or laboratory abnormalities. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
10.Symptoms or signs of gastrointestinal obstruction requiring parenteral nutrition or hydration or any other gastro-intestinal disorders or abnormalities, including difficulty swallowing, that would interfere with drug absorption.
11.Patient experienced = Grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities
12.Participant has had radiation therapy encompassing >20% of the bone marrow within 2 weeks prior to Day 1 of protocol therapy or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
13.Patient has a diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy
14.Patient has a known history of human immunodeficiency virus (type 1 or 2 antibodies).
15.Patient has known active hepatitis B or hepatitis C
16.Patient has an active autoimmune disease that has required systemic treatment in the past 2 years .Replacement therapy is not c
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method