Clinical Trials /

Japan Phase 2 Study of Niraparib in Patients With Advanced, Relapsed Ovarian Cancer

NCT03759600

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Japan Phase 2 Study of Niraparib in Patients With Advanced, Relapsed Ovarian Cancer
  • Official Title: A Phase 2, Multicenter, Open-label, Single-arm Study to Evaluate the Safety and Efficacy of Niraparib in Japanese Patients With Advanced, Relapsed, High-grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Have Received 3 or 4 Previous Chemotherapy Regimens

Clinical Trial IDs

  • ORG STUDY ID: Niraparib-2002
  • SECONDARY ID: U1111-1222-4100
  • SECONDARY ID: JapicCTI-184224
  • NCT ID: NCT03759600

Conditions

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Primary Peritoneal Cancer

Interventions

DrugSynonymsArms
NiraparibNiraparib 300 mg

Purpose

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.

Detailed Description

      The drug being tested in this study is called niraparib. Niraparib is being tested to treat
      people who have the homologous recombination deficiency (HRD)-positive, advanced, relapsed,
      high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer. This
      study will look at the efficacy and safety of niraparib in Japanese participants.

      The study will enroll approximately 16 participants. Participants will be enrolled to one
      group and after that will be asked to take niraparib capsules at the same time each day
      throughout the study:

      ・Niraparib 300 mg

      This multi-center trial will be conducted in Japan. The overall time to participate in this
      study is approximately 23 months. Participants will make multiple visits to the clinic in the
      treatment period, and the post-treatment period including follow-up assessments after the
      last dose of the study drug.
    

Trial Arms

NameTypeDescriptionInterventions
Niraparib 300 mgExperimentalNiraparib 300 milligrams (mg), capsules, orally, once daily on Days 1 - 28 of each 28-day treatment cycle.
  • Niraparib

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 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 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:

               1. Absolute neutrophil count (ANC) ≥1,500/μL.

               2. Platelet count ≥150,000/μL.

               3. Hemoglobin ≥10 g/dL.

               4. Serum creatinine ≤1.5× institutional upper limit of normal (ULN) OR calculated
                  creatinine clearance ≥50 mL/minute, using the Cockcroft-Gault equation.

               5. Total bilirubin ≤1.5×ULN OR direct bilirubin ≤1×ULN.

               6. 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:

               1. Are postmenopausal for at least 1 year before the screening visit, OR

               2. Are surgically sterile, OR

               3. 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

               4. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to approximately 23 months
Safety Issue:
Description:ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions; PR: At least a 30% decrease in sum of diameters (SoD) of target lesions, taking as a reference the baseline SoD.

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame:Up to approximately 23 months
Safety Issue:
Description:DOR is defined as the time from the first documented CR or PR per RECIST v. 1.1 to disease recurrence or objective disease progression whichever occurs first.
Measure:Disease Control Rate (DCR)
Time Frame:Up to approximately 23 months
Safety Issue:
Description:DCR is defined as the percentage of participants achieving CR, PR or Stable Disease (SD) as assessed by the Investigator per RECIST v. 1.1. SD: Defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: At least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm.
Measure:Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
Time Frame:Up to 30 days after the last dose (Approximately 23 months)
Safety Issue:
Description:An Adverse Event (AE) is defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Measure:Number of Participants with Grade 3 or Higher TEAEs
Time Frame:Up to 30 days after the last dose (Approximately 23 months)
Safety Issue:
Description:A severity grade is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE.
Measure:Number of Participants with Serious TEAEs
Time Frame:Up to 30 days after the last dose (Approximately 23 months)
Safety Issue:
Description:
Measure:Number of Participants with TEAEs Leading to Drug Discontinuation
Time Frame:Up to 30 days after the last dose (Approximately 23 months)
Safety Issue:
Description:
Measure:Number of Participants with TEAEs Leading to Dose Interruption
Time Frame:Up to 30 days after the last dose (Approximately 23 months)
Safety Issue:
Description:
Measure:Number of Participants with TEAEs Leading to Dose Reduction
Time Frame:Up to 30 days after the last dose (Approximately 23 months)
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:Up to approximately 23 months
Safety Issue:
Description:PFS is defined as the time from the first dose to the earlier of progression assessed by the Investigator per RECIST v. 1.1 (PD) or clinical criteria, or death due to any cause.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 23 months
Safety Issue:
Description:OS is defined as the time from the first dose to death due to any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Takeda

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