Metastatic pancreatic cancer
Conditions
Sponsors
Takeda Pharmaceutical Company Limited
Millennium Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Adult male or female participants aged >=20 years (Japan) or >=18 years (United States). 2.Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 3.Has pathologically confirmed metastatic pancreatic adenocarcinoma that has progressed after, at least, a first line of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed metastatic adenocarcinoma of the colon or rectum who have progressed to at least 2 lines of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed locally advanced or metastatic sqEC that has progressed after at least a first line of standard systemic therapy for metastatic disease. First-line participants can be enrolled if a platinum doublet is contraindicated or refused by the participants, OR pathologically confirmed locally advanced or metastatic sqNSCLC that has progressed after at least 2 lines of standard systemic therapy for metastatic disease. 4.For the Western safety cohort only: participants with locally advanced or metastatic solid tumor for whom no standard treatment with an established survival benefit is available or if the participant refuses other standard therapy. 5.For disease-specific cohort participants: measurable disease per RECIST V1.1 6.Left ventricular ejection fraction >50% as measured by echocardiogram (ECHO) or multiple gated acquisition (MUGA) scan within 4 weeks before receiving the first dose of study drug. 7.Recovered to Grade 1 or baseline from all toxic effects of previous therapy (except alopecia or neuropathy). 8.Suitable venous access for the study-required blood sampling. 9.For the Western safety cohort only: willingness to undergo serial skin tissue biopsies. 10.For disease-specific cohort participants: Must have an archival (banked) tumor sample or agree to have a new (fresh) tumor biopsy during the screening period. If a new tumor sample is needed, the disease should be accessible for a nonsignificant risk biopsy procedure (those occurring outside the brain, lung/mediastinum, and pancreas, or obtained with endoscopic procedures not extending beyond the stomach or bowel). For participants in the Western safety cohort, this biopsy is optional.
Exclusion criteria
Exclusion criteria: 1.Participants 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, such as phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine, or Saint John's wort within 14 days before the first dose of study drug. 3.Treatment with any systemic anticancer treatment (including investigational products) within 30 days or 5 half-lives, whichever is shorter, before the first dose of study drug. 4.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. - Significant, uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia). - New York Heart Association Class III to IV heart failure. - Any other cardiac condition that, in the opinion of the investigator, could pose an additional risk for participation in the study (e.g., pericardial effusion or restrictive cardiomyopathy). - Baseline prolongation of the QT interval corrected for heart rate (HR) using Fridericia's formula (QT interval corrected for heart rate using Fridericia's formula (QTcF); e.g., repeated demonstration of QTcF interval >480 millisecond (ms), history of congenital long QT syndrome, or torsades de pointes). 5.Hypertension that is unstable or not controlled by medication. 6.History of uncontrolled brain metastasis unless: - Previously treated with surgery, whole-brain radiation, or stereotactic radiosurgery, and - Stable disease (SD) for >=30 days, without steroid use (or stable steroid dose established for >=14 days before the first dose of TAK-931). 7.Known history of human immunodeficiency virus infection. 8.Known hepatitis B virus (HBV) surface antigen seropositive or detectable hepatitis C virus (HCV) infection viral load. Note: Participants who have positive HBV core antibody or HBV surface antigen antibody can be enrolled but must have an undetectable HBV viral load. 9.Prior treatment with radiation therapy involving >=25% of the hematopoietically active bone marrow within 3 months before the first dose of study drug. 10.Participants with known microsatellite instability-high (MSI-H) genotype or known wild type tumor protein 53 (TP53) per local testing. 11.Western Safety Cohort Only: Participants with Japanese heredity.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety Percentage of Participants with Dose Limiting Toxicities (DLTs) in Western Safety Cohort Timeframe; Cycle 1 (each cycle = 21 days) DLT: Any following event related to TAK-931 assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03; Non-febrile Grade 4 neutropenia lasting more than 7 consecutive days; Febrile neutropenia: Grade >=3 neutropenia with fever and/or infection; Grade 4 thrombocytopenia; Grade >=3 thrombocytopenia of any duration accompanied by Grade 2 bleeding or requiring transfusion; delay in the initiation of cycle 2 by more than 14 days due to a lack of adequate recovery of treatment-related hematological or nonhematologic toxicities; Grade 2 ejection fraction decreased by ECHO or MUGA scan; Grade 4 laboratory abnormalities; other Grade 2 nonhematologic toxicities considered by the investigator to be related to study drug and dose-limiting; Participants receiving =3 nonhematologic toxicity with the few exceptions: Grade 3 arthralgia/ myalgia, fatigue, laboratory abnormalities, nausea and/or emesis or diarrhea. safety Percentage of Participants with Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort Timeframe; From first dose of the study drug up to 30 days after the last dose (Up to approximately 15 months) An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. An SAE is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically i | — |
Secondary
| Measure | Time frame |
|---|---|
| pharmacokinetics Cmax: Maximum Observed Plasma Concentration for TAK-931 Timeframe; Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose pharmacokinetics Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 Timeframe; Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose pharmacokinetics AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931 Timeframe; Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose pharmacokinetics AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 Timeframe; Cycle 1 (each cycle = 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose pharmacokinetics CLr: Renal Clearance of TAK-931 Timeframe; Cycle 1 (each cycle = 21 days) Day 1 pre-dose and at multiple timepoints (up to 24 hours) post-dose CLr is a measure of apparent clearance of the drug from the urine. The clearance is the rate at which waste substances are cleared from the blood. pharmacokinetics t1/2z: Terminal disposition phase half-life Timeframe; Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose pharmacokinetics CLss/F: Steady-state Apparent Oral Clearance Timeframe; Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose CL/F is defined as apparent clearance of the drug from the plasma, calculated as the drug dose divided by AUC. pharmacokinetics Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCt) Timeframe; Cycle 1 (each cycle = 21 days) Day 8 pre-dose and at multiple timepoints (up to 24 hours) post-dose efficacy Overall Response Rate (CR and PR) Timeframe; Up to end of treatment (Up to approximately 14 months) Overall Respons | — |
Countries
Japan, North America
Outcome results
None listed