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

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04887194
• Other study ID #: 516-010
• Status: Completed
• Phase: Phase 1
• Start date: April 8, 2021
• Est. completion date: December 22, 2022

Study information

• Verified date: May 2024
• Source: Mirati Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 22, 2022
• Est. primary completion date: December 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor

Intervention

Drug:
• Sitravatinib
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
• Warfarin
CYP2C9 probe substrate
• Dextromethorphan
CYP2D6 probe substrate
• Midazolam
CYP3A4 probe substrate
• Digoxin
P-gp probe substrate
• Rosuvastatin
BCRP probe substrate
• Nivolumab
Nivolumab is a programmed death receptor (PD-1) blocking antibody

Locations

Country	Name	City	State
United States	NEXT Oncology	Austin	Texas
United States	NEXT Oncology	Fairfax	Virginia
United States	Goshen Health	Goshen	Indiana
United States	NEXT Oncology	San Antonio	Texas
United States	MultiCare Health System	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Part 1; 1-20 Days
Primary	PK parameters of probe drugs; AUC from time zero to infinity (AUC8)	(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib	Part 1; 1-20 Days
Primary	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	Part 1; 1-20 Days
Primary	Adverse Events	Characterization of AEs by incidence, severity, timing, seriousness & relationship to study treatment	Through study completion, an average of 12 months
Secondary	Plasma PK parameters of sitravatinib and M10; C-max	C-max	1-20 Days
Secondary	Plasma PK parameters of sitravatinib and M10; AUC over the dosing interval (AUC)	AUC over the dosing interval (AUC)	1-20 Days
Secondary	Plasma PK parameters of sitravatinib and M10; trough plasma concentration (C-trough)	trough plasma concentration (C-trough)	1-20 Days
Secondary	Plasma PK parameters of sitravatinib and M10; time to maximum concentration (t-max)	time to maximum concentration (t-max)	1-20 Days
Secondary	Adverse Events	Safety characterized by type, incidence, severity, timing, seriousness & relationship to study treatment of adverse events, and laboratory abnormalities	1-20 Days
Secondary	QT/QTc	ECG data	Part 1: Pre-dose to Day 10 (QTc cohort); Part 1: Pre-dose to Day14 (DDI cohort)