Clinical Trials /

Japan Phase 2 Study of Niraparib (Maintenance Therapy) in Patients With Relapsed Ovarian Cancer

NCT03759587

Description:

The purpose of this study is to evaluate the safety and efficacy of niraparib in Japanese participants with platinum-sensitive, relapsed ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who achieved complete response (CR) or partial response (PR) in the last chemotherapy containing platinum-based anticancer agents.

Related Conditions:
  • Fallopian Tube Carcinoma
  • High Grade Fallopian Tube Serous Adenocarcinoma
  • Ovarian Carcinoma
  • Ovarian Serous Tumor
  • Primary Peritoneal Carcinoma
  • Primary Peritoneal Serous Adenocarcinoma
  • Primary Peritoneal Serous Papillary Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Japan Phase 2 Study of Niraparib (Maintenance Therapy) in Patients With Relapsed Ovarian Cancer
  • Official Title: A Phase 2, Multicenter, Open-label, Single-arm Study to Evaluate the Safety of Niraparib in Japanese Patients With Platinum-sensitive, Relapsed Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Achieved CR or PR in the Last Chemotherapy Containing Platinum-based Anticancer Agents

Clinical Trial IDs

  • ORG STUDY ID: Niraparib-2001
  • SECONDARY ID: U1111-1222-4074
  • SECONDARY ID: JapicCTI-184225
  • NCT ID: NCT03759587

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 Japanese participants with platinum-sensitive, relapsed ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who achieved complete response (CR) or partial response (PR) in the last chemotherapy containing platinum-based anticancer agents.

Detailed Description

      The drug being tested in this study is called niraparib. Niraparib is being tested to treat
      people who have platinum-sensitive, relapsed ovarian cancer, fallopian tube cancer, or
      primary peritoneal cancer. This study will look at the safety and efficacy of niraparib in
      Japanese participants.

      The study will enroll approximately 15 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 28 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. Participant must have a histologically diagnosed ovarian cancer, fallopian tube
             cancer, or primary peritoneal cancer.

          4. Participant must have a high-grade (or Grade 3) serous or high-grade predominantly
             serous histology or known to have germline breast cancer gene mutation (gBRCAmut).

          5. Participants must have completed at least 2 previous lines of platinum-containing
             therapy (eg, carboplatin, oxaliplatin, or cisplatin):

        Note: The last platinum regimen did not necessarily have to immediately follow the
        next-to-last (penultimate) platinum regimen. For example, if a participant received a
        non-platinum regimen between the penultimate platinum regimen and last platinum regimen,
        she could have been eligible as long as she met all entry criteria.

          1. For the penultimate platinum-based chemotherapy prior to study enrollment,
             participants must have had platinum-sensitive disease after this treatment, defined as
             achieving a response (CR or PR) and disease progression >6 months after completion of
             her last dose of platinum therapy (documented 6 to 12 months or >12 months). Source
             documentation was required.

          2. For the last line of platinum-based chemotherapy prior to study enrollment:

        i. Participants must have received a platinum-containing regimen for a minimum of 4 cycles.

        ii. Participants must have achieved a partial or complete tumor response. iii. Following
        the last regimen, participants must have had either.

          1. CA-125 in the normal range, OR

          2. CA-125 decrease by more than 90% during the last platinum regimen, and which was
             stable for at least 7 days (ie, no increase >15%).

        iv. Following the last regimen, participants could not have had any measurable lesion >2 cm
        at the time of study enrollment.

        c. Participants must have been enrolled within 8 weeks after completion of their final dose
        of the platinum-containing regimen.

        6. Participants must have performance status of ≤1 on the Eastern Cooperative Oncology
        Group (ECOG) Performance Status Scale.

        7. Participants must have adequate organ function as indicated by the following laboratory
        values:

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

          2. Platelet count ≥100,000/μL.

          3. Hemoglobin ≥9 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.

             8. Participants must be able to take oral medications. 9. 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.

             10. Female participants who:

        a. Are postmenopausal for at least 1 year before the screening visit, OR b. Are surgically
        sterile, OR c. 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 d. 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 drainage of ascites during last 2 cycles of last
             chemotherapy.

          2. Participants who have had palliative radiotherapy encompassing >20% of the bone marrow
             within 1 week of the first dose of study treatment.

          3. Participants who have any known, persistent (>4 weeks), Grade ≥3 toxicity from last
             cancer therapy.

          4. 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.

          5. Participants who have known hypersensitivity to the components of niraparib.

          6. Participants who have had prior treatment with a known poly (adenosine diphosphate
             [ADP]-ribose) polymerase (PARP) inhibitor.

          7. Participant who have had treatment with any investigational products within 28 days or
             5 half-lives (whichever was longer) before the first dose.

          8. 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.

          9. 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.

         10. 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.

         11. Participants who have received a transfusion (platelets or red blood cells) within 4
             weeks of the first dose of study treatment.

         12. Participants who have received a live virus or bacterial vaccines within 4 weeks of
             the first dose of study treatment.

         13. 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.

         14. 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.

         15. 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.

         16. Participants who are immunocompromised (participants with splenectomy are allowed).

         17. Participants who have known human immunodeficiency virus (HIV) positive.

         18. 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:Number of Participants with Grade 3 or 4 Thrombocytopenia Occurring within 30 Days after Initial Administration of Niraparib
Time Frame:Up to 30 days after the initial dose (Approximately 6 to 8 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 Adverse Events (AE).

Secondary Outcome Measures

Measure:Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
Time Frame:Up to 30 days after the last dose (Approximately 28 months)
Safety Issue:
Description:An 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 28 months)
Safety Issue:
Description:A severity grade is defined by the 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 28 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 28 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 28 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 28 months)
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:Up to approximately 28 months
Safety Issue:
Description:PFS is defined as the time from the study enrollment to the earlier of progression assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Progression Disease [PD]) or clinical criteria, or death due to any cause. PD: At least a 20% increase in the SoD (Sum of Diameters) 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:Overall Survival (OS)
Time Frame:Up to approximately 28 months
Safety Issue:
Description:OS is defined as the time from the study enrollment to death due to any cause.
Measure:Overall Response Rate (ORR)
Time Frame:Up to approximately 28 months
Safety Issue:
Description:ORR is defined as the percentage of participants achieving CR and PR per RECIST version 1.1. CR: Disappearance of all target lesions; PR: At least a 30% decrease in SoD of target lesions, taking as a reference the baseline SoD.

Details

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

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