Advanced Solid Tumor
Conditions
Brief summary
Study 516-010 is an open-label Phase 1, drug-drug interaction and QTc study evaluating the effect of sitravatinib on probe substrates for CYP450 enzymes and BCRP and P-gp transporters.
Detailed description
Part 1 of this study is designed to evaluate the potential for drug-drug interactions and QTc effects with sitravatinib monotherapy when administered with probe drugs for specific cytochrome P450 (CYP) enzymes (CYP2C9, CYP2D6, and CYP3A4) and P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters Part 2 allows for patients to continue sitravatinib treatment with the addition of the checkpoint inhibitor Nivolumab.
Interventions
DRUGSitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
DRUGWarfarin
CYP2C9 probe substrate
DRUGDextromethorphan
CYP2D6 probe substrate
DRUGMidazolam
CYP3A4 probe substrate
DRUGDigoxin
P-gp probe substrate
DRUGRosuvastatin
BCRP probe substrate
DRUGNivolumab
Nivolumab is a programmed death receptor (PD-1) blocking antibody
Sponsors
Mirati Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Two Part, Phase 1 study enrolling patients with advanced tumor types into two cohorts: drug-drug interaction (DDI) and QTc. All patients receive the same anticancer treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of unresectable advanced/metastatic solid tumor * Life expectancy of at least 3 months * Adequate bone marrow and organ function
Exclusion criteria
* Ongoing medical condition or need for treatment with medication that may affect the PK of study treatments during Part 1 * Immunocompromising conditions * Impaired heart function * Active or prior documented autoimmune disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters of probe drugs; AUC from time zero to the last data point (AUC-last) | Part 1; 1-20 Days | (warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib |
| PK parameters of probe drugs; AUC from time zero to infinity (AUC∞) | Part 1; 1-20 Days | (warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib |
| PK parameters of probe drugs; C-max | Part 1; 1-20 Days | (warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib |
| Adverse Events | Through study completion, an average of 12 months | Characterization of AEs by incidence, severity, timing, seriousness & relationship to study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 1-20 Days | Safety characterized by type, incidence, severity, timing, seriousness & relationship to study treatment of adverse events, and laboratory abnormalities |
| Plasma PK parameters of sitravatinib and M10; C-max | 1-20 Days | C-max |
| QT/QTc | Part 1: Pre-dose to Day 10 (QTc cohort); Part 1: Pre-dose to Day14 (DDI cohort) | ECG data |
| Plasma PK parameters of sitravatinib and M10; AUC over the dosing interval (AUC) | 1-20 Days | AUC over the dosing interval (AUC) |
| Plasma PK parameters of sitravatinib and M10; trough plasma concentration (C-trough) | 1-20 Days | trough plasma concentration (C-trough) |
| Plasma PK parameters of sitravatinib and M10; time to maximum concentration (t-max) | 1-20 Days | time to maximum concentration (t-max) |
Countries
United States
Outcome results
None listed