PK Study to Assess Drug-drug Interaction and QTc Between Sitravatinib and a Cocktail of Substrates

Mirati Therapeutics Inc.40 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumor

Interventions

SitravatinibDRUG

Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases

WarfarinDRUG

CYP2C9 probe substrate

DextromethorphanDRUG

CYP2D6 probe substrate

Midazolam

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (5)

Goshen Health

Goshen, Indiana, United States

NEXT Oncology

Austin, Texas, United States

NEXT Oncology

San Antonio, Texas, United States

NEXT Oncology

Fairfax, Virginia, United States

MultiCare Health System

Outcomes

Primary Outcomes

PK parameters of probe drugs; AUC from time zero to the last data point (AUC-last)

(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib

Time frame: Part 1; 1-20 Days

PK parameters of probe drugs; AUC from time zero to infinity (AUC∞)

(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib

Time frame: Part 1; 1-20 Days

PK parameters of probe drugs; C-max

(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib

Time frame: Part 1; 1-20 Days

Adverse Events

Characterization of AEs by incidence, severity, timing, seriousness \& relationship to study treatment

Time frame: Through study completion, an average of 12 months

Secondary Outcomes

Plasma PK parameters of sitravatinib and M10; C-max

C-max

Time frame: 1-20 Days

Plasma PK parameters of sitravatinib and M10; AUC over the dosing interval (AUC)

AUC over the dosing interval (AUC)

Time frame: 1-20 Days

Plasma PK parameters of sitravatinib and M10; trough plasma concentration (C-trough)

trough plasma concentration (C-trough)

Data from ClinicalTrials.gov

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