metastatic or recurrent endometrial or ovarian carcinosarcoma MedDRA version: 21.1 Level: PT Classification code 10057529 Term: Ovarian cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 100
Conditions
Interventions
Trade Name: NIRAPARIB
Product Name: NIRAPARIB
Pharmaceutical Form: Capsule
INN or Proposed INN: NIRAPARIB
CAS Number: 1038915-60-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concent
Sponsors
ARCAGY-GINECO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 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 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
Exclusion criteria
Exclusion criteria: 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase II - Selection Phase :To select the best experimental strategy between TSR-042 combined with Niraparib and Niraparib in monotherapy. Phase III:To compare the overall survival in patients with metastatic or recurrent endometrial or ovarian carcinosarcoma after at least a first line of chemotherapy between the best experimental strategy and chemotherapy alone. ;Secondary Objective: To further assess the overall safety profile of the best experimental arm compared to CT alone To compare the anti-tumor activity between the best experimental strategy and chemotherapy alone To compare the clinical benefit between the best experimental strategy and chemotherapy alone To compare the PFS2 (time from randomization to second progression) between the best experimental strategy and chemotherapy alone •To compare the effects of treatments on patient reported outcomes & QoL ;Primary end point(s): Selection Phase – Phase II •Response Rate at 4 months (W16-RR) as per RECIST 1.1 Phase III •Overall survival (OS). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety and tolerability; • Progression-free survival (PFS) based on Investigator assessment per RECIST v1.1; • Time from randomization to second progression (PFS2) based on Investigator assessment per RECIST v1.1; • Overall response rate (ORR) based on Investigator assessment per RECIST v1.1; • Duration of response (DoR) based on Investigator assessment per RECIST v1.1; • Time To Subsequent Therapy (TTST). • Patient-reported Outcomes (PRO): QoL QLQ-C30 modules OV-28, HADS and PRO CTCAEs 1) Assessment of the effect of validated QOL tools to examine the effect of therapy on patients’ life, using the European Organization for Research and Treatment of Cancer (EORTC) QOL disease-specific module. 2) Concurrent evaluation of the impact of anxiety and depression on QOL and toxicity through the Hospital Anxiety and Depression Scale (HADS). 3) Definition of the reliability of the physician evaluation of the toxicity compared to patient point of view using PRO-CTCAE questionnaire, offering the unique opportunity to validate these tools in different European countries. | — |
Countries
France
Contacts
Public ContactAurélie PAILHE, Project Manager
ARCAGY-GINECO
Outcome results
None listed