Advanced solid tumor
Conditions
Sponsors
Takeda Pharmaceutical Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Japanese male or female participants aged 20 years or older on the day of signing informed consent. 2. Participants must have a cytologically- or histologically-confirmed metastatic or locally advanced solid tumor and have failed or progressed after standard therapy, or for which standard therapy does not exist in the opinion of the investigator. 3. Participants must have Performance Status of =1500/microL -Platelet count: >=100,000/microL -Hemoglobin: >=9 g/dL b. Kidney -Serum creatinine: =50 mL/min (as calculated using the Cockcroft Gault equation or measured using 24-hour urine creatinine clearance) for participants with creatinine levels >=1.5xinstitutional ULN. c. Liver -Total bilirubin in serum: <=1.5xULN (except in participants with Gilbert's syndrome). Participants with Gilbert's syndrome may be enrolled if the participant's direct bilirubin is <=1.5xULN of the direct bilirubin. -Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): <=2.5 xULN OR <=5xULN if participants have liver metastases. d. Coagulation (does not pertain to participants receiving anticoagulants) -Prothrombin time (PT): <=1.2xULN -Activated partial thromboplastin time (aPTT): <=1.2xULN 5. 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 one highly effective method of contraception and one 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.) Male participants, even if surgically sterilized (ie, vasectomy), who: -Agree to practice effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug. If the female partner of a male participant is of child bearing potential, it should also be advised to use a highly effective method of contraception, 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 for the female partner], condoms only, withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.) 6. 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.
Exclusion criteria
Exclusion criteria: 1. Participant who have received chemotherapy, radiotherapy, hormonal or biological therapy within 14 days (within 28 days for anticancer monoclonal antibody, within 42 days for nitrosoureas or mitomycin C) prior to Cycle 1 Day 1. If the participant has residual toxicity from prior chemotherapy treatment, such toxicity must be <=Grade 1 (NOTE: participants with Grade 2 alopecia may qualify for this study). If bevacizumab had been used in the past, all bevacizumab-related toxicities must have resolved. Participants with prostate cancer may have been treated with luteinizing hormone-releasing hormone (LH-RH) analogs. 2. Participants who received a known or putative poly (ADP-ribose) polymerase (PARP) inhibitor or other drugs that may inhibit the PARP, either as part of a clinical trial or as standard of care. 3. Participants who initiated bisphosphonate therapy or are adjusting bisphosphonate dose/regimen within 30 days prior to Cycle 1 Day 1. Participants on a stable bisphosphonate regimen are eligible and may continue the treatment. 4. Treatment with any investigational products within 28 days or 5 half-lives (whichever was longer) before Cycle 1 Day 1. 5. Participants who have symptomatic ascites or a symptomatic pleural effusion. A participant who is treated and clinically stable for these conditions is eligible. 6. Participants with a known primary central nervous system (CNS) tumor. 7. Participants with known CNS metastases and/or carcinomatous meningitis are excluded. However, participants with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 30 days prior to Cycle 1 Day 1 defined as: (1) no evidence of new or enlarging CNS metastases, (2) off steroids, or (3) on a stable dose and administration of steroids. 8. Participants who have a hypersensitivity to the components of the study drugs or their analogs. 9. Participants who are considered to be at high medical risk due to a serious, uncontrolled disease, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days prior to Cycle 1 Day 1) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, uncontrolled hypertension, or any psychiatric disorder that prohibits obtaining informed consent. 10. Participants who have a history or current evidence of any condition, therapy, or lab abnormality 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. 11. Known gastrointestinal (GI) disease or GI surgery that could interfere with the GI absorption of study drug, such as difficulty swallowing capsules and total gastrectomy. 12. Participants who have a psychiatric disorder that may interfere with the conduct of the trial. 13. Participant is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the past year) of drug or alcohol abuse. 14. Participants who are pregnant or breast-feeding, or expecting to conceive or be a father of children within the planned duration of the study. NOTE: If a breast-feeding woman discontinue breast-feeding, she may be enrolled in the study. 15. Known human immunodeficiency virus positive. 16. K
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety Number of Participants with a Dose Limiting Toxicity (DLT) Time Frame: Baseline up to Day 21 in Cycle 1 (Cycle length=21 days) DLT was evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), v4.03 and defined as any of the following events occurring during Cycle 1 that were considered by investigator to be related with niraparib: Any Grade 5 or 4 hematologic toxicity, except Grade 4 neutropenia less than () 38.5 degree Celsius and/or infection requiring antibiotic/anti-fungal treatment; Any Grade 3, 4,or 5 non-hematologic toxicity except: Grade 3 nausea, vomiting, diarrhea/dehydration occurring in setting of inadequate compliance with supportive care and lasting 14 days. safety Number of Participants with TEAEs Time Frame: From first dose of study drug up to 28 days after the last dose of study drug (up to Cycle 22 Day 49) (Cycle length =21 days) safety Number of Participants with Grade 3 or Higher TEAEs Time Frame: From first dose of study drug up to 28 days after the last dose of study drug (up to Cycle 22 Day 49) (Cycle length =21 days) TEAEs were graded as per the NCI-CTCAE version 4.03. As per the NCI-CTCAE, Grade 1 (mild, asymptomatic or mild symptoms); Grade 2 (moderate, minimal, local or noninvasive intervention indicated); Grade 3 (severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (life-threatening consequences, urgent intervention indicated); Grade 5 (death related to adverse event [AE]). safety Number of Participants with Serious TEAEs Time Frame: From first dose of study drug up to 28 days after the last dose of study drug (up to Cycle 22 Day 49) (Cycle length =21 days) safety Number of Participants who Discontinued Study Drug due to TEAEs Time Frame: From first dose of study drug up to 28 days after the last dose of study drug (up to Cycle 22 Day 49) (Cycle length =21 days) | — |
Secondary
| Measure | Time frame |
|---|---|
| pharmacokinetics Cmax: Maximum Observed Plasma Concentration for Niraparib Time Frame: Cycle 1 Day 1 and 21: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =21 days) pharmacokinetics Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Niraparib Time Frame: Cycle 1 Days 1 and 21: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =21 days) pharmacokinetics AUC24: Area under the Plasma Concentration-Time Curve from Time 0 to Time 24 for Niraparib Time Frame: Cycle 1 Days 1 and 21: pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =21 days) | — |
Countries
Japan
Outcome results
None listed