A randomized, double-blind, phase 3 comparison of Platinum-based therapy with tsr042 and niraparib Versus standard of care platinum-based therapy as first-line treatment of stage iii or iv nonmucinous epithelial ovarian cancer.
- Patients must be female, ≥18 years of age, able to understand the study procedures, and agree to participate in the study by providing written informed consent.
- Patients with a histologically confirmed diagnosis of high-grade non-mucinous epithelial ovarian cancer (serous, endometrial, clear cell, carcinosarcoma, and mixed pathologies) that is Stage III or IV according to the FIGO or tumor, node and metastasis staging criteria [ie, American Joint Committee on Cancer].
- All patients with Stage IV disease are eligible. This includes those with inoperable disease, those who undergo PDS (R0 or macroscopic disease), or those for whom NACT is planned.
- Patients with Stage III are eligible if they meet one or more of the following criteria:
a) Stage IIIC patients with CC0 resection if they meet the following criteria: Aggregate ≥5 cm extra-pelvic disease during PDS as assessed by the Investigator
b) All patients with inoperable Stage III disease
c) All Stage III patients with macroscopic residual tumor (per Investigator judgement) following PDS
d) All Stage III patients for whom NACT is planned.
- Patients must provide a blood sample for ctDNA HRR testing at Pre-Screening or Screening. The ctDNA HRR testing results will be used for patient stratification.
- Patient must provide a tumor tissue sample at Pre-Screening or Screening for HRD testing from either archival tumor tissue or fresh biopsy tissue.
- Patients of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin) within 3 days prior to receiving the first dose of study treatment.
- Patients must be postmenopausal, free from menses for >1 year, surgically sterilized, or willing to use highly effective contraception to prevent pregnancy (see Appendix 3) or must agree to abstain from activities that could result in pregnancy throughout the study, starting with enrollment through 180 days after the last dose of study treatment.
- Patients must have adequate organ function, defined as follows (Note: CBC test should be obtained without transfusion or receipt of stimulating factors within 2 weeks before obtaining Screening blood sample):
a) ANC ≥1,500/μL
b) Platelet count ≥100,000/μL
c) Hemoglobin ≥9 g/dL
d) Serum creatinine ≤1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation
e) Total bilirubin ≤1.5 × ULN or direct bilirubin ≤1.5 × ULN
f) AST and ALT ≤2.5 × ULN unless liver metastases are present, in which case they must be ≤5 × ULN
- Patients must have an ECOG score of 0 or 1.
- Patients must have normal BP or adequately treated and controlled hypertension (systolic BP ≤140 mmHg and/or diastolic BP ≤90 mmHg).
- Patients must agree to complete HRQoL questionnaires throughout the study.
- Patients must be able to take oral medication.
- Patient has mucinous, germ cell, transitional cell, or undifferentiated tumor.
- Patient has low-grade or Grade 1 epithelial ovarian cancer.
- Stage III patient with R0 resection after PDS (ie, no macroscopic residual disease, unless inclusion criterion #4a is met).
- Patient has not adequately recovered from prior major surgery.
- Patient has a known condition, therapy, or laboratory abnormality that might confound the study results or interfere with the patient’s participation for the full duration of the study treatment in the opinion of the Investigator.
- Patient is pregnant or is expecting to conceive children while receiving study drug or for up to 180 days after the last dose of study drug. Patient is breastfeeding or is expecting to breastfeed within 30 days of receiving the final dose of study drug (women should not breastfeed or store breastmilk for use, during niraparib treatment and for 30 days after receiving the final dose of study treatment).
- Patient has known active central nervous system metastases, carcinomatous meningitis, or both.
- 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, New York Heart Association 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).
- Patient has a bowel obstruction by clinical symptoms or CT scan, subocclusive mesenteric disease, abdominal or gastrointestinal fistula, gastrointestinal perforation, or intra-abdominal abscess.
- Patient receiving bevacizumab as SOC has proteinuria as demonstrated by urine protein:creatinine ratio ≥1.0 at Screening or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick at baseline should undergo a 24-hour urine collection and must demonstrate <2 g of protein in 24 hours to be eligible).
Deelnemende centra: UMCU, Erasmus MC, UMCG, AMC
Studie is net geopend voor inclusie in Nederland (UMCG).