advanced cancer Advanced solid tumors
Conditions
Interventions
Part 1: 80 mg single dose on Day1 and Day 3 respectively followed by 50 mg QD
thereafter.
Part 2: Tablet single dose providing an AUC comparable to the 80-mg single dose
of PIC on Day 1, Day 3, and
Sponsors
Millenium Pharmaceuticals
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Adult patients with histologically or cytologically confirmed metastatic or locally advanced or metastatic solid tumors for whom there is no available standard treatment with proven survival benefit, this therapy is not indicated, or it is refused by the patient. 2. Eastern Cooperative Oncology Group performance status of 0 to 1. 3. Adequate bone marrow reserve and renal and hepatic function based on the following laboratory parameters: * Absolute neutrophil count *1.5 × 109/L, platelet count *75.0 × 109/L, and hemoglobin *85 g/L. * Total bilirubin *1.5 times the institutional upper limit of the normal range (ULN) or total bilirubin <3.0 times ULN in patients with well documented Gilbert*s Syndrome. * Serum alanine aminotransferase or aspartate aminotransferase *3.0 times the ULN (<5 times ULN if liver enzyme elevations are due to hepatocellular cancer, biliary tract cancer, or metastatic disease in the liver). * Creatinine <1.5 times the institutional ULN or estimated creatinine clearance using the Cockcroft-Gault formula *30 mL/min for patients with serum creatinine concentrations above institutional limits. 4. Left ventricular ejection fraction *50% as measured by echocardiogram or multiple gated acquisition scan within 4 weeks before receiving the first dose of study drug. 5. Recovered to Grade 1 or baseline from all toxic effects of previous therapy (except alopecia or neuropathy).
Exclusion criteria
Exclusion criteria: 1. Patients who require continuous use of PPIs or histamine-2 receptor antagonists and patients 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, enzalutamide, mitotane, ritonavir, rifampin, or St John's wort within 14 days before the first dose of study drug. 3. Treatment with systemic anticancer treatments or any investigational products within 28 days before the first dose of study drug or 5 half-lives, whichever is shorter. 4. Patients with hypertension that is unstable or not controlled despite appropriate medical therapy. 5. Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging or computed tomography) during the screening period. 6. Known history of HIV infection. 7. Known hepatitis B (HBV) surface antigen seropositive or detectable hepatitis C infection viral load. Note: Patients who have positive hepatitis B core antibody or hepatitis B surface antigen antibody can be enrolled but must have an undetectable hepatitis B viral load. 8. Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption of study drug, such as total gastrectomy or GI conditions that could substantially modify gastric pH or GI transit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 * Ratio of geometric mean of the following PK parameters for TAK-931 tablets in reference to PIC and associated 90% CIs: * Maximum observed concentration (Cmax). * AUC from time 0 to time of the last quantifiable concentration (AUClast). * AUC from time 0 to infinity (AUC*). Part 2 * Ratio of geometric mean of the following PK parameters for TAK-931 tablets under fed and fasted conditions and associated 90% CIs: * Cmax. * AUClast. * AUC*. * Ratio of geometric mean of the following PK parameters for TAK-931 tablets in the presence and absence of esomeprazole and associated 90% CIs: * Cmax. * AUClast. * AUC*. * Summary statistics of the following PK parameters for TAK-931: * Cmax. * AUClast. * AUC*. | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1 * PK parameters of TAK-931 following single-dose administrations as PIC and tablets at 80 mg: * Time of first occurrence of Cmax (tmax). * Apparent clearance after extravascular administration (CL/F). * Terminal disposition phase half-life (t1/2z). * Antitumor activity: * Overall response rate (ORR). * PFS. * Disease control rate (DCR). * Duration of response (DOR). * Safety: * Percentage of serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), Grade *3 TEAEs, TEAEs leading to discontinuation or dose modification, and percentage of laboratory abnormalities. Part 2 * PK parameters: * tmax, CL/F, and t1/2z of TAK-931 tablets following single-dose administration under fasting and fed conditions. * tmax, CL/F, and t1/2z of TAK-931 tablets following single-dose administration in the absence and in the presence of esomeprazole. * Antitumor activity: * ORR. * PFS. * DCR. * DOR. * Safety: * Percentage of serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), Grade *3 TEAEs, TEAEs leading to discontinuation or dose modification, and percentage of laboratory abnormalities. | — |
Countries
Netherlands
Outcome results
None listed