Clinical trial NCT04887194: PK Study to Assess Drug-drug Interaction and QTc Between Sitravatinib and a Cocktail of Substrates
Official title: A Two-cohort, Two-part, Phase 1, Multicenter, Open-label, Fixed-sequence, Drug-Drug Interaction and QTc Assessments of Sitravatinib Followed by Combination Treatment With Nivolumab in Patients With Advanced Solid Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2021-05-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: PK parameters of probe drugs; AUC from time zero to the last data point (AUC-last)
timeFrame: Part 1; 1-20 Days
measure: PK parameters of probe drugs; AUC from time zero to infinity (AUC∞)
timeFrame: Part 1; 1-20 Days
measure: PK parameters of probe drugs; C-max
timeFrame: Part 1; 1-20 Days
measure: Adverse Events
timeFrame: Through study completion, an average of 12 months
Secondary outcomes:
measure: Plasma PK parameters of sitravatinib and M10; C-max
timeFrame: 1-20 Days
measure: Plasma PK parameters of sitravatinib and M10; AUC over the dosing interval (AUC)
timeFrame: 1-20 Days
measure: Plasma PK parameters of sitravatinib and M10; trough plasma concentration (C-trough)
timeFrame: 1-20 Days
measure: Plasma PK parameters of sitravatinib and M10; time to maximum concentration (t-max)
timeFrame: 1-20 Days
measure: Adverse Events
timeFrame: 1-20 Days
measure: QT/QTc
timeFrame: Part 1: Pre-dose to Day 10 (QTc cohort); Part 1: Pre-dose to Day14 (DDI cohort)
Other outcomes:
Locations:
city: Goshen
country: United States
facility: Goshen Health
state: Indiana
city: Austin
country: United States
facility: NEXT Oncology
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
city: Tacoma
country: United States
facility: MultiCare Health System
state: Washington
Study officials:
affiliation: Mirati Therapeutics Inc.
name: Curtis Chin, MD
role: STUDY_DIRECTOR
References: