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

NCT ID: NCT03759600

Last Updated: 2024-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-26
• Study Completion Date: 2022-12-28

Brief 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.

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.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Niraparib 300 mg

Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1 to 28 of each 28-day treatment cycle for up to 50 cycles.

Group Type: EXPERIMENTAL

Niraparib

Intervention Type: DRUG

Niraparib capsule

Interventions

Niraparib

Niraparib capsule

Intervention Type: DRUG

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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, Japan

Hirosaki University Hospital

Hirosaki, Aomori, Japan

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

The Jikei University Kashiwa Hospital

Kashiwa, Chiba, Japan

Shikoku Cancer Center

Matsuyama, Ehime, Japan

Ehime University Hospital

Tōon, Ehime, Japan

Kurume University Hospital

Kurume, Fukuoka, Japan

Kure Medical Center and Chugoku Cancer Center

Kure, Hiroshima, Japan

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Sapporo Medical University Hospital

Sapporo, Hokkaido, Japan

Hyogo Cancer Center

Akashi, Hyōgo, Japan

Kansai Rosai Hospital

Amagasaki, Hyōgo, Japan

Iwate Medical University Hospital

Morioka, Iwate, Japan

Tokai University Hospital

Isehara, Kanagawa, Japan

Nippon Medical School Musashi Kosugi Hospital

Kawasaki, Kanagawa, Japan

Mie University Hospital

Tsu, Mie-ken, Japan

Tohoku University Hospital

Sendai, Miyagi, Japan

University of the Ryukyus Hospital

Nakagami-gun, Okinawa, Japan

Kindai University Hospital

Sayama, Osaka, Japan

Saitama Medical University International Medical Center

Hidaka, Saitama, Japan

Shizuoka Cancer Center

Nagaizumi-cho, Shizuoka, Japan

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Cancer Institute Hospital

Koto-ku, Tokyo, Japan

The Jikei University Hospital

Minato-ku, Tokyo, Japan

Toho University Omori Medical Center

Ōta-ku, Tokyo, Japan

Keio University Hospital

Shinjuku-ku, Tokyo, Japan

Chiba Cancer Center

Chiba, , Japan

Chiba University Hospital

Chiba, , Japan

Gifu University Hospital

Gifu, , Japan

Kagoshima City Hospital

Kagoshima, , Japan

Kyoto University Hospital

Kyoto, , Japan

Nagasaki University Hospital

Nagasaki, , Japan

Niigata University Medical & Dental Hospital

Niigata, , Japan

Countries

Japan

References

Aoki D, Tabata T, Yanagida S, Nakamura T, Kondo E, Hamanishi J, Harano K, Hasegawa K, Hirasawa T, Hori K, Komiyama S, Matsuura M, Nakai H, Nakamura H, Sakata J, Takehara K, Takekuma M, Yokoyama Y, Kase Y, Sumino S, Soeda J, Kato A, Suri A, Okamoto A, Sugiyama T. Niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer: final results of a multicenter phase 2 study. J Gynecol Oncol. 2024 Sep;35(5):e114. doi: 10.3802/jgo.2024.35.e114.

Reference Type: DERIVED

PMID: 39251349 (View on PubMed)

Okamoto A, Kondo E, Nakamura T, Yanagida S, Hamanishi J, Harano K, Hasegawa K, Hirasawa T, Hori K, Komiyama S, Matsuura M, Nakai H, Nakamura H, Sakata J, Tabata T, Takehara K, Takekuma M, Yokoyama Y, Kase Y, Sumino S, Soeda J, Suri A, Aoki D, Sugiyama T. Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. J Gynecol Oncol. 2021 Mar;32(2):e16. doi: 10.3802/jgo.2021.32.e16. Epub 2020 Dec 10.

Reference Type: DERIVED

PMID: 33327047 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1222-4100

Identifier Type: OTHER

Identifier Source: secondary_id

JapicCTI-184224

Identifier Type: REGISTRY

Identifier Source: secondary_id

Niraparib-2002

Identifier Type: -

Identifier Source: org_study_id