Clinical Trials /

Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer

NCT02219711

Description:

MGCD516 is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR, DDR2, TRK and Eph families. In this study, MGCD516 is orally administered to patients with advanced solid tumor malignancies to evaluate its safety, pharmacokinetic, metabolism, pharmacodynamic and clinical activity profiles. During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed; during the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based upon having a tumor type, including but not limited to, non small cell lung cancer and head and neck cancer positive for specific activating MET, NTRK2, NTRK3, or DDR2 mutations, MET or KIT/PDGFRA/KDR gene amplification, selected gene rearrangements involving the MET, RET, AXL, NTRK1, or NTRK3 gene loci, or having loss of function mutations in the CBL gene. In addition patients with clear cell renal cell carcinoma refractory to angiogenesis inhibitors or metastatic prostate cancer with bone metastasis will be enrolled.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02219711

Trial Eligibility

Document

Title

  • Brief Title: Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer
  • Official Title: A Phase 1/1b Study of MGCD516 in Patients With Advanced Solid Tumor Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 516-001
  • NCT ID: NCT02219711

Conditions

  • Advanced Cancer

Interventions

DrugSynonymsArms
MGCD516SitravatinibMGCD516

Purpose

MGCD516 is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR, DDR2, TRK and Eph families. In this study, MGCD516 is orally administered to patients with advanced solid tumor malignancies to evaluate its safety, pharmacokinetic, metabolism, pharmacodynamic and clinical activity profiles. During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed; during the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based upon having a tumor type, including but not limited to, non small cell lung cancer and head and neck cancer positive for specific activating MET, NTRK2, NTRK3, or DDR2 mutations, MET or KIT/PDGFRA/KDR gene amplification, selected gene rearrangements involving the MET, RET, AXL, NTRK1, or NTRK3 gene loci, or having loss of function mutations in the CBL gene. In addition patients with clear cell renal cell carcinoma refractory to angiogenesis inhibitors or metastatic prostate cancer with bone metastasis will be enrolled.

Detailed Description

      During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed.

      During the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected
      patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based
      upon the following cancer diagnosis:

      Non-small cell lung cancer with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA,
      KIT or CBL.

      Head and neck squamous cell carcinoma with genetic alterations in MET.

      Clear cell renal cell carcinoma refractory to angiogenesis inhibitors.

      Metastatic prostate cancer with bone metastases.

      Other cancer diagnosis having a selected genetic alteration in MGCD516 target RTKs.

Trial Arms

NameTypeDescriptionInterventions
MGCD516ExperimentalMGCD516 oral capsule, administered in escalating doses in Phase 1, beginning with daily dosing and exploring other regimens as necessary, in 21 or 28 days cycles
  • MGCD516

Eligibility Criteria

        Inclusion Criteria:

          -  Metastatic or unresectable solid tumor malignancy

          -  Standard treatment is not available

          -  Adequate bone marrow and organ function

        Exclusion Criteria:

          -  History of a significant cardiovascular illness

          -  Prolonged corrected QT (QTc) interval

          -  Left ventricular ejection fraction < 40%

          -  Symptomatic or uncontrolled brain metastases

          -  Other active cancer
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Type of dose limiting adverse event
Time Frame:Up to 3 weeks on treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Kind of metabolites of MGCD516 in blood plasma
Time Frame:Up to 9 weeks on treatment
Safety Issue:
Description:
Measure:Concentration of selected marker proteins in blood plasma
Time Frame:Up to 9 weeks on treatment
Safety Issue:
Description:Proteins include VEGF A, soluble VEGF-R2 and soluble MET
Measure:Percent of patients having objective disease response to treatment
Time Frame:Up to 1 year on treatment
Safety Issue:
Description:Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Mirati Therapeutics Inc.

Trial Keywords

  • MGCD516
  • MET
  • AXL
  • RET
  • TRK
  • NTRK
  • DDR2
  • KDR
  • VEGFR
  • PDGFRA
  • KIT
  • Tyrosine kinase inhibitor
  • NSCLC
  • Non-small cell lung cancer
  • Head and neck cancer
  • Renal cell carcinoma
  • Prostate cancer
  • Phase 1
  • CBL
  • Sitravatinib

Last Updated

January 30, 2020