A Phase II Randomized, Open Label Non-inferiority Study of NiraParib Maintenance After 3 vs. 6 Cycles of Platinum-based Chemotherapy in completeLy debUlked Advanced HRDpositive High-grade Ovarian Cancer patientS in First Line Therapy

Inclusion Criteria28

• Written informed consent and obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
• Female patient, age ≥ 18 years.
• FIGO Stage III-IV high-grade ovarian cancer (all histological types, except mucinous histology)
• Complete primary debulked patients (without any macroscopic residuals), confirmed by CT-Scan postoperatively.
• Patients must have formalin-fixed, paraffin-embedded tumor samples available from the primary cancer for central NGS analysis and must be HRDpositive defined as BRCAmut independent of NOGGO GIS Score OR NOGGO GIS Score \>83 independent of BRCA status, based on these results.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Patients must be able to take oral medications.
• Synchronous and secondary malignancies are allowed if the prognosis of the ovarian cancer is not affected. The investigator must contact the medical monitoring team before enrolling the patient in the clinical trial.
• Patients must have normal organ and bone marrow function:
• Hemoglobin ≥ 10.0 g/dL independent of transfusion ≤ 14 days prior to screening hemoglobin assessment
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); \< 2 × ULN if hyperbilirubinemia is due to Gilbert's syndrome
• Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) ≤ 2,5 x ULN
• Serum creatinine ≤ 1.5 x institutional ULN and creatinine clearance \> 30 mL/min.
• Postmenopausal or evidence of non-childbearing status for women of childbearing potential prior to the first dose of study treatment. Female patients of childbearing potential must have a negative serum pregnancy test result ≤3 days prior to administration of the first dose of study treatment.
• Patients are considered to be of childbearing potential unless 1 of the following applies:
• Considered to be permanently sterile. Permanent sterilization includes hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy; or
• Is postmenopausal, defined as no menses for at least 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 mIU/mL or higher) may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to confirm a postmenopausal state.
• Female patients of reproductive potential must practice highly effective methods (failure rate \< 1% per year) of contraception with their partners, if of reproductive potential, during treatment and for 6 months following the last dose of chemotherapy or the last dose of niraparib, whichever occurs later, or longer if requested by local authorities. Highly effective contraception includes: Ongoing use of progesterone only injectable or implantable contraceptives; Placement of an intrauterine device (IUD) or intrauterine system (IUS); Bilateral tubal occlusion; Sexual abstinence as defined as complete or true abstinence, acceptable only when it is the usual and preferred lifestyle of the patient; periodic abstinence (e.g., calendar, symptothermal, post-ovulation methods) is not acceptable; or Sterilization of the male partner, with appropriate post-vasectomy documentation of absence of sperm in ejaculate.
• Participation in another clinical study with an investigational product immediately prior to randomization. Earliest time point for randomization is after the time required for the investigational product to undergo 5 half-lives has passed.
• Has a known history of Human Immunodeficiency Virus (HIV) infection (known HIV1/HIV2 antibodies positive) or acquired immunodeficiency syndrome (AIDS) related illness.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] has been detected) infection.
• Has active infection with SARS-CoV-2 (antigen test).
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of chemotherapy treatment and while and 28 days after the last dose of trial treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. Administration of inactivated vaccines is allowed.
• Patient has contraindications listed in the most recent SmPC.
• Patient who might be dependent on the sponsor, CRO, site or the investigator.
• \. In Germany: Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40a S. 1 Nr. 2 AMG.