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

Phase 1

Completed

• Conditions: Advanced Cancer
• Interventions: Drug: MGCD516

• Registration Number: NCT02219711
• Lead Sponsor: Mirati Therapeutics Inc.

Brief Summary

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.

Study Timeline

• Study Start: 2014-08
• Study First Submitted: 2014-08-14
• Study First Submitted QC: 2014-08-15
• Study First Posted: 2014-08-19
• Primary Completion: 2022-04-27
• Study Completion: 2022-04-27
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-02
• Last Update Posted: 2023-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 193

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MGCD516	MGCD516	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

Primary Outcome Measures

Name	Time	Method
Peak Plasma Concentration (Cmax) of MGCD516	Up to 72 hours
Type of dose limiting adverse event	Up to 3 weeks on treatment
Area under the plasma concentration versus time curve (AUC) of MGCD516	Up to 72 hours

Secondary Outcome Measures

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

Trial Locations

Locations (43)

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

University of California, San Diego; 🇺🇸 San Diego, California, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Sarcoma Oncology Research Center; 🇺🇸 Santa Monica, California, United States

Innovative Clinical Research Institute; 🇺🇸 Whittier, California, United States

Rocky Mountain Cancer Center; 🇺🇸 Denver, Colorado, United States

Holy Cross Michael & Dianne Bienes Comprehensive Cancer Center; 🇺🇸 Fort Lauderdale, Florida, United States

Florida Cancer Affiliates; 🇺🇸 Ocala, Florida, United States

Florida Cancer Specialists; 🇺🇸 Sarasota, Florida, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

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