Nonhematologic Neoplasms, Advanced
Conditions
Sponsors
Takeda Pharmaceutical Company Limited
Millennium Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of an advanced, nonhematologic/solid tumor (with the exception of primary brain tumor). 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 . 3. Patients for whom no effective standard therapy is available. 4. Life expectancy of >=3 months. 5. Female participants who: - Are postmenopausal (natural amenorrhea and not due to other medical reasons) for at least 1 year before the screening visit, OR - Are surgically sterile, OR - If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 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 subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.) Male participants, even if surgically sterilized (eg, status postvasectomy), who: - Agree to practice effective barrier contraception during the entire study treatment period and through 120 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 subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.) - Agree not to donate sperm during this study and for 120 days after receiving their last dose of study drug. 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of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care. 7. Ability to swallow oral medications, willingness to undergo serial skin punch biopsies, and suitable venous access for the study-required PK and pharmacodynamic sampling. 8. Clinical laboratory values as specified below within 28 days before the first dose of study drug: - Bone marrow reserve consistent with absolute neutrophil count (ANC) >=1500/mm3,platelet count >=100,000/mm3, and hemoglobin >=9 g/dL. - Total bilirubin must be 1.5 times the upper limit of normal (ULN). - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be 3=3.0 g/dL. - Serum creatinine 50% as measured by ECHO or MUGA within 4 weeks before receiving the first dose of study drug. 10. Recovered (Grade 1 toxicity) from the reversible effects of prior anticancer therapy. Patients with ongoing toxicities at baseline may be eligible; however, any Grade 2 baseline toxicity (except for alopecia) should be discussed with the medical monitor.
Exclusion criteria
Exclusion criteria: 1. Patients who require continuous use of proton pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists and participants who are taking PPIs within 5 days before the first dose of study drug. 2. Treatment with clinically significant enzyme inducers (see Appendix G) within 14 days before the first dose of study drug. 3. Treatment with any investigational products within 30 days before the first dose of study drug. 4. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug. 5. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. 6. History of any of the following within the last 3 months before administration of the first dose of study drug: - Ischemic myocardial event including angina requiring therapy and artery revascularization procedures, myocardial infarction, and unstable symptomatic ischemic heart disease. - Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures. - Thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events). - Significant, uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia). - Use of rate control drugs for arrhythmias (including beta blockers [such as metoprolol],acetylcholine, digoxin, and non-dihydropyridine calcium channel blockers diltiazem and verapamil). - Placement of a pacemaker for control of cardiac rhythm. - Requirement for inotropic support (including digoxin). - New York Heart Association Class II to IV heart failure (Appendix F). - Any other cardiac condition that in the opinion of the investigator could pose an additional risk for the participation in the study (eg, pericardial effusion or restrictive cardiomyopathy). - Baseline prolongation of the rate-corrected QT interval (QTc; eg, repeated demonstration of QTc interval >480 msec, or history of congenital, long QT syndrome, or torsades de pointes). 7. Patients with any of the following blood pressure conditions: - History of orthostatic hypotension or syncope that required medical intervention.Orthostatic hypotension is defined as a 20 mmHg fall in systolic blood pressure and/or a 10 mmHg fall in diastolic blood pressure within 2 to 5 minutes of quiet standing immediately after a 5-minute period of supine rest. - Postural orthostatic tachycardia syndrome (POTS) or postural tachycardia syndrome (defined as an increase in heart rate of >30 beats per minute over baseline after 10 minutes of quiet standing). - Hypertension that is unstable or not controlled by medication. 8. Seizures requiring antiepileptic treatment. 9. History of uncontrolled brain metastasis unless: - Previously treated with surgery, whole-brain radiation, or stereotactic radiosurgery. - Stable disease for >=60 days, without steroid use (or stable steroid dose established for >=28 days before the first dose of TAK-931). 10. Symptomatic and/or progressive central nervous system (CNS) metastases. 11. Ongoing medical conditions, such as acute exacerbations of chronic illnesses, seriousinfections, or major surgery within 4 weeks before receiving the first dose of study drug. 12. Known history of human immunodeficiency virus (HIV) infection. 13.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety Number and Percentage of Participants With Dose-Limiting Toxicities (DLTs) Assessed by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Version 4.03 Time Frame: Baseline up to Cycle 1 (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) Toxicity was evaluated by NCI CTCAE v4.03. DLT:any of following occurred events during Cycle 1 considered by investigator to be possibly related to therapy:1)Grade4 neutropenia,2)Febrile neutropenia lasting greater(>)1 hour,3)Grade greater than or equal to (>=)3 neutropenia with infection,4)Grade >=3 thrombocytopenia with bleeding,4)Grade 4 thrombocytopenia,5)delay in initiation of Cycle 2 by >14 days,6)Grade 2:=3 nonhematologic toxicity except arthralgia/myalgia and fatigue, isolated >=Grade 3 laboratory abnormalities if it is asymptomatic and resolves to <=Grade 1 or baseline levels in <=7 days;inadequately treated Grade 3 nausea and/or vomiting and diarrhea. safety Number of Participants with Reporting one or More Treatment-emergent Adverse Events (TEAEs) Time Frame: Baseline up to 30 days after the last dose of study drug or before initiation of new anti-cancer therapy (up to Day 499) | — |
Secondary
| Measure | Time frame |
|---|---|
| pharmacokinetics Cmax: Maximum Observed Plasma Concentration After First Dose of TAK-931 Time Frame: Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) pharmacokinetics Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) After First Dose of TAK-931 Time Frame: Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) pharmacokinetics AUC 24: Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours After First Dose of TAK-931 Time Frame: Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) pharmacokinetics AUC 12: Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours After Multiple Doses of TAK-931 Time Frame: Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8 and 12 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) pharmacokinetics AUC last: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration After First Dose of TAK-931 Time Frame: Cycle 1 Day 1: pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) pharmacokinetics Cmax: Maximum Observed Plasma Concentration After Multiple Doses of TAK-931 Time Frame: Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycle length= 21 days [Schedules A, D and E] and 28 days [Schedule B]) pharmacokinetics Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) After Multiple Doses of TAK-931 Time Frame: Cycle 1 Day 8 (Schedule A and D), Cycle 1 Day 7 (Schedule B), Cycle 1 Day 9 (Schedule E): pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose (Cycl | — |
Countries
Japan
Outcome results
None listed