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:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Phase 1/1b Study of <span class="go-doc-concept go-doc-intervention">MGCD516</span> in Patients With Advanced Cancer

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

    NCT ID: NCT02219711

    ORG ID: 516-001

    Trial Conditions

    Advanced Cancer

    Trial Interventions

    Drug Synonyms Arms
    MGCD516 MGCD516

    Trial 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, or selected gene rearrangements involving the MET, RET, AXL, NTRK1, or
    NTRK3 gene loci. 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
    or KIT.

    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

    Name Type Description Interventions
    MGCD516 Experimental MGCD516 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 < 50%

    - Symptomatic or uncontrolled brain metastases

    - Other active cancer

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Type of dose limiting adverse event

    Area under the plasma concentration versus time curve (AUC) of MGCD516

    Peak Plasma Concentration (Cmax) of MGCD516

    Secondary Outcome Measures

    Kind of metabolites of MGCD516 in blood plasma

    Concentration of selected marker proteins in blood plasma

    Percent of patients having objective disease response to treatment

    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