| Eligibility |
Inclusion Criteria:
1. Written informed consent and obtained from the subject prior to performing any
protocol-related procedures, including screening evaluations.
2. Female patient, age = 18 years.
3. FIGO Stage III-IV high-grade ovarian cancer (all histological types, except mucinous
histology)
4. Complete primary debulked patients (without any macroscopic residuals), confirmed by
CT-Scan postoperatively.
5. Patients must have formalin-fixed, paraffin-embedded tumor samples available from the
primary cancer for central NGS analysis and must be BRCAm OR LOHhigh (cut-off of 16%
or more genomic LOH), independent of BRCA status, based on these results.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
7. Patients must be able to take oral medications.
8. 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.
9. Patients must have normal organ and bone marrow function:
1. Hemoglobin = 10.0 g/dL independent of transfusion = 14 days prior to screening
hemoglobin assessment
2. Absolute neutrophil count (ANC) = 1.5 x 109/L
3. Platelet count = 100 x 109/L
4. Total bilirubin = 1.5 x institutional upper limit of normal (ULN); < 2 × ULN if
hyperbilirubinemia is due to Gilbert's syndrome
5. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT))
and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) =
2,5 x ULN
6. Serum creatinine = 1.5 x institutional ULN and creatinine clearance > 30 mL/min.
10. 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:
1. Considered to be permanently sterile. Permanent sterilization includes hysterectomy,
bilateral salpingectomy, and/or bilateral oophorectomy; or
2. 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.
Exclusion Criteria:
1. Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (i.e., germ
cell tumors) and Ovarian tumors of low malignant potential (e.g., borderline tumors),
or mucinous carcinoma of the ovary.
2. Low-grade ovarian, fallopian tube or peritoneal cancer.
3. Has known hypersensitivity to any of the study drugs or any of the excipients of any
of the study drugs.
4. Has known hypersensitivity to platin-containing compounds other than carboplatin.
5. Patients posttransplant, including previous allogeneic bone marrow transplant.
6. Has undergone interval debulking of the tumor.
7. Has received any anti-cancer therapy for ovarian cancer other than primary surgery.
8. Administration of other simultaneous chemotherapy drugs, any other anti-cancer therapy
or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial
treatment period (hormonal replacement therapy is permitted as are steroidal
antiemetics).
9. Has received prior treatment with a PARP inhibitor or has participated in a trial
where any treatment arm included the administration of a PARP inhibitor.
10. Bevacizumab is planned to be given together with first line chemotherapy or as
maintenance.
11. Clinically significant cardiovascular disease:
1. Cerebrovascular accident or myocardial infarction or unstable angina =6 months
before start of study treatment
2. Severe cardiac arrhythmia (recent event or active or uncontrolled)
3. New York Heart Association grade =2 congestive heart failure
4. Uncontrolled hypertension (defined as systolic blood pressure >140 mmHg and/or
diastolic blood pressure >90 mmHg), or history of hypertensive crisis, or
hypertensive encephalopathy or posterior reversible encephalopathy syndrome
5. History of stroke or transient ischemic attack =6 months before start of study
treatment
6. Coronary/peripheral artery bypass graft =6 months before start of study treatment
7. Deep vein thrombosis or thromboembolic events =1 month before start of study
treatment
12. History or evidence of brain metastases or spinal cord compression.
13. Known history of MDS or a pre-treatment cytogenetic testing result at risk for a
diagnosis of MDS/AML.
14. Current, clinically relevant bowel obstruction at the time of randomization.
15. Patients with gastrointestinal disorders likely to interfere with absorption of the
study medication.
16. Pregnant or lactating women, women of child-bearing potential who do not agree to the
usage of highly effective contraception methods (see inclusion criteria) starting with
the screening visit through at least 6 months after the last dose of chemotherapy
treatment or through at least 1 month after the last dose of niraparib, whichever
occurs later.
17. 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.
18. Has a known history of Human Immunodeficiency Virus (HIV) infection (known HIV1/HIV2
antibodies positive) or acquired immunodeficiency syndrome (AIDS) related illness.
19. 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.
20. Has active infection with SARS-CoV-2 (antigen test).
21. Patient who might be dependent on the sponsor, CRO, site or the investigator.
22. In Germany: Patient who has been incarcerated or involuntarily institutionalized by
court order or by the authorities § 40a S. 1 Nr. 2 AMG.
|
