Japan Phase 2 Study of Niraparib in Participants With Advanced, Relapsed Ovarian Cancer
Condition: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms
Intervention: Niraparib
Intervention description: Niraparib capsule
Intervention MeSH terms: Niraparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: Female
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The purpose of this study is to evaluate the safety and efficacy of niraparib in participants
      with advanced, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary
      peritoneal cancer who have received 3 or 4 previous chemotherapy regimens.
    

Eligibility criteria:

        Inclusion Criteria

          1. Japanese female participants aged 20 years or older on the day of signing informed
             consent.

          2. Voluntary written consent must be given before performance of any study related
             procedure not part of standard medical care, with the understanding that consent may
             be withdrawn by the participant at any time without prejudice to future medical care.

          3. Participants must agree to undergo tumor homologous recombination deficiency/deficient
             (HRD) testing, and this test result must show that participants have an HRD-positive
             tumor (defined by the presence of a deleterious or suspected deleterious breast cancer
             gene (BRCA) mutation or be positive for genomic instability) by the central laboratory
             selected by the sponsor.

             Note 1: The study HRD test result must be received prior to enrollment. The tumor
             sample may be submitted for HRD testing prior to the screening period (ie, within 40
             days before Cycle 1 Day 1) if the consent has been obtained and it appears the
             participant is likely to meet other eligibility requirements.

             Note 2: If historic blood germline BRCA mutation (gBRCAmut) is detected by a prior
             gBRCAmut testing, then tumor HRD sample test results are not required prior to
             enrollment; however, HRD testing still needs to be performed.

          4. Participants must have histologically diagnosed, relapsed, high-grade (Grade 2 or 3)
             serous epithelial ovarian, fallopian tube, or primary peritoneal cancer with recurrent
             disease and must have been previously treated with chemotherapy and have not
             experienced disease progression at least 6 months to the last chemotherapy containing
             platinum-based anticancer agents.

          5. Participants must have completed 3 or 4 previous chemotherapy regimens. Participants
             must have completed their last chemotherapy regimen >4 weeks prior to treatment
             initiation.

          6. Participants must have at least one measurable disease according to Response
             Evaluation Criteria in Solid Tumors (RECIST) (v.1.1).

          7. Participants must have performance status of ≤1 on the Eastern Cooperative Oncology
             Group (ECOG) Performance Status Scale.

          8. Participants must have adequate organ function as indicated by the following
             laboratory values:

               -  Absolute neutrophil count (ANC) ≥1,500/μL.

               -  Platelet count ≥150,000/μL.

               -  Hemoglobin ≥10 g/dL.

               -  Serum creatinine ≤1.5× institutional upper limit of normal (ULN) OR calculated
                  creatinine clearance ≥50 mL/minute, using the Cockcroft-Gault equation.

               -  Total bilirubin ≤1.5×ULN OR direct bilirubin ≤1×ULN.

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN
                  unless liver metastases were present, in which case they had to be ≤5×ULN.

          9. Participants must have formalin-fixed, paraffin-embedded tumor samples available from
             the primary or recurrent cancer or agree to undergo fresh biopsy prior to study
             treatment initiation.

         10. Participants must be able to take oral medications.

         11. Female participants of childbearing potential must be negative for pregnancy test
             (beta-human chorionic gonadotropin [β-hCG]) within 7 days prior to receiving the first
             dose of study treatment.

         12. Female participants who:

               -  Are postmenopausal for at least 1 year before the screening visit, OR

               -  Are surgically sterile, OR

               -  If they are of childbearing potential, agree to practice 1 highly effective
                  method of contraception and 1 additional effective (barrier) method at the same
                  time, from the time of signing the informed consent through 180 days after the
                  last dose of study drug, OR

               -  Agree to practice true abstinence, when this is in line with the preferred and
                  usual lifestyle of the participant. (Periodic abstinence [eg, calendar,
                  ovulation, symptothermal, postovulation methods], condoms only, withdrawal,
                  spermicides only, and lactational amenorrhea are not acceptable methods of
                  contraception. Female and male condoms should not be used together.)

        Exclusion Criteria

          1. Participants who have had palliative radiotherapy encompassing >20% of the bone marrow
             within 1 week of the first dose of study treatment.

          2. Participants who have any known, persistent (>4 weeks), Grade ≥3 hematologic toxicity
             from last cancer therapy.

          3. Participants who have any known, persistent (>4 weeks), Grade ≥3 fatigue during the
             last cancer therapy.

          4. Participants who have received pelvic radiotherapy as treatment for primary or
             recurrent disease within 1 year of the first dose of study treatment.

          5. Participants who have symptomatic, uncontrolled brain or leptomeningeal metastases.

             To be considered "controlled," central nervous system (CNS) disease must have
             undergone treatment (eg, radiation or chemotherapy) at least 1 month prior to study
             enrollment. The participant must not have had any new or progressive signs or symptoms
             related to the CNS disease and must have been taking a stable dose of steroids or no
             steroids (as long as these were started at least 4 weeks prior to enrollment] or no
             steroids). A scan to confirm the absence of brain metastases at baseline was not
             required. Participants with spinal cord compression might have been considered if they
             had received definitive treatment for this and evidence of clinically stable disease
             for 28 days.

          6. Participants who have known hypersensitivity to the components of niraparib.

          7. Participants who have had prior treatment with a known poly (adenosine diphosphate
             [ADP]-ribose) polymerase (PARP) inhibitors.

          8. Participant who have had treatment with any investigational products within 28 days or
             5 half-lives (whichever was longer) before the first dose.

          9. Participants who have had major surgery per Investigator judgment within 3 weeks of
             the first dose. Participant must have recovered from any effects of any major surgery.

         10. Participants who have diagnosis, detection, or treatment of invasive second primary
             malignancy other than ovarian cancer ≤24 months prior to study enrollment (except
             basal or squamous cell carcinoma of the skin that was definitively treated). Note:
             Participants must not have any known history or current diagnosis of myelodysplastic
             syndrome (MDS) or acute myeloid leukemia (AML), irrespective of the time for disease
             history.

         11. Participants who are considered a poor medical risk due to a serious, uncontrolled
             medical disorder, non-malignant systemic disease, or active, uncontrolled infection.
             Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent
             (within 90 days of the first dose) myocardial infarction, uncontrolled major seizure
             disorder, unstable spinal cord compression, superior vena cava syndrome, small bowel
             obstruction or other serious gastrointestinal disorder, or any psychiatric disorder
             that prohibits obtaining informed consent.

         12. Participants who have received a transfusion (platelets or red blood cells) within 4
             weeks of the first dose of study treatment.

         13. Participants who have received a live virus or bacterial vaccines within 4 weeks of
             the first dose of study treatment.

         14. Participants who have a history or current evidence of any condition, therapy, or lab
             abnormality (including active or uncontrolled myelosuppression [ie, anemia,
             leukopenia, neutropenia, thrombocytopenia]) that might confound the results of the
             study, interfere with the participant's participation throughout the study period, or
             study participation is not in the best interest of the participant.

         15. Participants who are regular user (including "recreational use") of any illicit drugs
             at the time of signing informed consent or have a recent history (within the past
             year) of drug or alcohol abuse.

         16. Participants who are pregnant or breast-feeding or expecting to conceive within the
             planned duration of the study.

             NOTE: If a breast-feeding woman discontinue breast-feeding, she may be enrolled in the
             study.

         17. Participants who are immunocompromised (participants with splenectomy are allowed).

         18. Participants who have known human immunodeficiency virus (HIV) positive.

         19. Participants who have known hepatitis B surface antigen (HBsAg) positive, or known or
             suspected active hepatitis C virus (HCV) infection.

        NOTE: Participants who are positive for hepatitis B core antibody (HBcAb) or hepatitis B
        surface antibody (HBsAb) can be enrolled but must have an undetectable hepatitis B virus
        (HBV) viral load. Participants who have positive hepatitis C virus antibody (HCVAb) must
        have an undetectable HCV viral load.