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Completed

NCT Number: NCT04887194

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

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.

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Key information

Conditions

Advanced Solid Tumor

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Goshen Health, Goshen, Indiana, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sitravatinib

Drug

Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases

Other names: MGCD516

Warfarin

Drug

CYP2C9 probe substrate

Other names: Coumadin

dextromethorphan

Drug

CYP2D6 probe substrate

Other names: Robitussin

midazolam

Drug

CYP3A4 probe substrate

Other names: Versed

Digoxin

Drug

P-gp probe substrate

Other names: LANOXICAPS

Rosuvastatin

Drug

BCRP probe substrate

Other names: Crestor

Nivolumab

Drug

Nivolumab is a programmed death receptor (PD-1) blocking antibody

Other names: OPDIVO

Primary outcomes

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

    Time frame: 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

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

    Time frame: 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

  3. PK parameters of probe drugs; C-max

    Time frame: 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

  4. Adverse Events

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

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

Secondary outcomes

  1. Plasma PK parameters of sitravatinib and M10; C-max

    Time frame: 1-20 Days

    C-max

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

    Time frame: 1-20 Days

    AUC over the dosing interval (AUC)

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

    Time frame: 1-20 Days

    trough plasma concentration (C-trough)

  4. Plasma PK parameters of sitravatinib and M10; time to maximum concentration (t-max)

    Time frame: 1-20 Days

    time to maximum concentration (t-max)

  5. Adverse Events

    Time frame: 1-20 Days

    Safety characterized by type, incidence, severity, timing, seriousness & relationship to study treatment of adverse events, and laboratory abnormalities

  6. QT/QTc

    Time frame: Part 1: Pre-dose to Day 10 (QTc cohort); Part 1: Pre-dose to Day14 (DDI cohort)

    ECG data

Sponsors and collaborators

Lead sponsor

Mirati Therapeutics Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
May 14, 2021
Registry last updated
May 8, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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