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

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ClinicalTrials.gov Identifier: NCT03759600
Recruitment Status : Not yet recruiting
First Posted : November 30, 2018
Last Update Posted : December 7, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda

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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer Drug: Niraparib Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : December 4, 2018
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : November 30, 2020


Arm Intervention/treatment
Experimental: Niraparib 300 mg
Niraparib 300 milligrams (mg), capsules, orally, once daily on Days 1 - 28 of each 28-day treatment cycle.
Drug: Niraparib
Niraparib capsule




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to approximately 23 months ]
    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 :
  1. Duration of Response (DOR) [ Time Frame: Up to approximately 23 months ]
    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.

  2. Disease Control Rate (DCR) [ Time Frame: Up to approximately 23 months ]
    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.

  3. Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to 30 days after the last dose (Approximately 23 months) ]
    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.

  4. Number of Participants with Grade 3 or Higher TEAEs [ Time Frame: Up to 30 days after the last dose (Approximately 23 months) ]
    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.

  5. Number of Participants with Serious TEAEs [ Time Frame: Up to 30 days after the last dose (Approximately 23 months) ]
  6. Number of Participants with TEAEs Leading to Drug Discontinuation [ Time Frame: Up to 30 days after the last dose (Approximately 23 months) ]
  7. Number of Participants with TEAEs Leading to Dose Interruption [ Time Frame: Up to 30 days after the last dose (Approximately 23 months) ]
  8. Number of Participants with TEAEs Leading to Dose Reduction [ Time Frame: Up to 30 days after the last dose (Approximately 23 months) ]
  9. Progression Free Survival (PFS) [ Time Frame: Up to approximately 23 months ]
    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.

  10. Overall Survival (OS) [ Time Frame: Up to approximately 23 months ]
    OS is defined as the time from the first dose to death due to any cause.



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03759600


Contacts
Contact: Takeda Study Registration Call Center +1-877-825-3327 medicalinformation@tpna.com

Locations
Japan
Aichi Cancer Center Hospital Not yet recruiting
Nagoya, Aichi, Japan
Hirosaki University Hospital Not yet recruiting
Hirosaki, Aomori, Japan
National Cancer Center Hospital East Not yet recruiting
Kashiwa, Chiba, Japan
The Jikei University Kashiwa Hospital Not yet recruiting
Kashiwa, Chiba, Japan
Shikoku Cancer Center Not yet recruiting
Matsuyama, Ehime, Japan
Ehime University Hospital Not yet recruiting
Toon, Ehime, Japan
Kurume University Hospital Not yet recruiting
Kurume, Fukuoka, Japan
Hokkaido University Hospital Not yet recruiting
Sapporo, Hokkaido, Japan
Sapporo Medical University Hospital Not yet recruiting
Sapporo, Hokkaido, Japan
Hyogo Cancer Center Not yet recruiting
Akashi, Hyogo, Japan
Kansai Rosai Hospital Not yet recruiting
Amagasaki, Hyogo, Japan
Iwate Medical University Hospital Not yet recruiting
Morioka, Iwate, Japan
Tokai University Hospital Not yet recruiting
Isehara, Kanagawa, Japan
Nippon Medical School Musashi Kosugi Hospital Not yet recruiting
Kawasaki, Kanagawa, Japan
Mie University Hospital Not yet recruiting
Tsu, Mie, Japan
Tohoku University Hospital Not yet recruiting
Sendai, Miyagi, Japan
University of the Ryukyus Hospital Not yet recruiting
Nakagami-gun, Okinawa, Japan
Kindai University Hospital Not yet recruiting
Osakasayama, Osaka, Japan
Saitama Medical University International Medical Center Not yet recruiting
Hidaka, Saitama, Japan
Shizuoka Cancer Center Not yet recruiting
Nagaizumi-cho, Shizuoka, Japan
National Cancer Center Hospital Not yet recruiting
Chuo-ku, Tokyo, Japan
Cancer Institute Hospital Not yet recruiting
Koto-ku, Tokyo, Japan
The Jikei University Hospital Not yet recruiting
Minato-ku, Tokyo, Japan
Toho University Omori Medical Center Not yet recruiting
Ota-ku, Tokyo, Japan
Keio University Hospital Not yet recruiting
Shinjuku-ku, Tokyo, Japan
Chiba Cancer Center Not yet recruiting
Chiba, Japan
Gifu University Hospital Not yet recruiting
Gifu, Japan
Kagoshima City Hospital Not yet recruiting
Kagoshima, Japan
Kyoto University Hospital Not yet recruiting
Kyoto, Japan
Nagasaki University Hospital Not yet recruiting
Nagasaki, Japan
Niigata University Medical & Dental Hospital Not yet recruiting
Niigata, Japan
Sponsors and Collaborators
Takeda
Investigators
Study Director: Study Director Takeda

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT03759600     History of Changes
Other Study ID Numbers: Niraparib-2002
U1111-1222-4100 ( Other Identifier: WHO )
JapicCTI-184224 ( Registry Identifier: JapicCTI )
First Posted: November 30, 2018    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Ovarian Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents