Clinical Trials /

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

NCT04887194

Description:

Study 516-010 is an open-label Phase 1, drug-drug interaction study evaluating the effect of sitravatinib on probe substrates for CYP450 enzymes and BCRP and P-gp transporters.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT04887194

Trial Eligibility

Document

Title

  • Brief Title: PK Study to Assess Drug-drug Interaction Between Sitravatinib and a Cocktail of Substrates
  • Official Title: Two-part, Phase 1, Multicenter, Open-label, Fixed-sequence, Drug-Drug Interaction Study to Investigate the Effect of Sitravatinib on Probe Substrates Followed by Combination Treatment With Nivolumab in Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 516-010
  • NCT ID: NCT04887194

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
SitravatinibMGCD516Phase 1, Part 1 Drug-Drug Interaction with sitravatinib monotherapy
WarfarinCoumadinPhase 1, Part 1 Drug-Drug Interaction with sitravatinib monotherapy
DextromethorphanRobitussinPhase 1, Part 1 Drug-Drug Interaction with sitravatinib monotherapy
MidazolamVersedPhase 1, Part 1 Drug-Drug Interaction with sitravatinib monotherapy
DigoxinLANOXICAPSPhase 1, Part 1 Drug-Drug Interaction with sitravatinib monotherapy
RosuvastatinCrestorPhase 1, Part 1 Drug-Drug Interaction with sitravatinib monotherapy
NivolumabOPDIVOPhase 1, Part 2 Combination Therapy

Purpose

Study 516-010 is an open-label Phase 1, drug-drug interaction 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 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.

Trial Arms

NameTypeDescriptionInterventions
Phase 1, Part 1 Drug-Drug Interaction with sitravatinib monotherapyExperimentalTo evaluate the potential for drug-drug interactions (DDI) with sitravatinib monotherapy. To determine the effect of sitravatinib on the pharmacokinetics (PK) of midazolam (CYP3A4 probe substrate), warfarin (CYP2C9 probe substrate), dextromethorphan (CYP2D6 probe substrate), rosuvastatin (BCRP probe substrate), and digoxin (P-gp probe substrate).
  • Sitravatinib
  • Warfarin
  • Dextromethorphan
  • Midazolam
  • Digoxin
  • Rosuvastatin
Phase 1, Part 2 Combination TherapyExperimentalTo evaluate safety and tolerability of Sitravatinib treatment with the addition of the checkpoint inhibitor nivolumab.
  • Sitravatinib
  • 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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:PK parameters of probe drugs (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
Safety Issue:
Description:AUC from time zero to the last data point (AUC-last)

Secondary Outcome Measures

Measure:Plasma PK parameters of sitravatinib and M10
Time Frame:1-20 Days
Safety Issue:
Description:C-max
Measure:Plasma PK parameters of sitravatinib and M10
Time Frame:1-20 Days
Safety Issue:
Description:AUC over the dosing interval (AUC)
Measure:Plasma PK parameters of sitravatinib and M10
Time Frame:1-20 Days
Safety Issue:
Description:trough plasma concentration (C-trough)
Measure:Plasma PK parameters of sitravatinib and M10
Time Frame:1-20 Days
Safety Issue:
Description:time to maximum concentration (t-max)
Measure:Adverse Events
Time Frame:1-20 Days
Safety Issue:
Description:Safety characterized by type, incidence, severity, timing, seriousness & relationship to study treatment of adverse events, and laboratory abnormalities
Measure:Objective disease response
Time Frame:Through study completion, an average of 12 months
Safety Issue:
Description:Measured in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and duration of response (DOR)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mirati Therapeutics Inc.

Last Updated

May 14, 2021