Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 193
- Metastatic or unresectable solid tumor malignancy
- Standard treatment is not available
- Adequate bone marrow and organ function
- 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)
Guthrie Clinical Research
🇺🇸Sayre, Pennsylvania, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Alabama
🇺🇸Birmingham, Alabama, United States
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
Holy Cross Michael & Dianne Bienes Comprehensive Cancer Center
🇺🇸Fort Lauderdale, Florida, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Maryland Oncology Hematology,
🇺🇸Rockville, Maryland, United States
Washington University Center for Advanced Medicine
🇺🇸Saint Louis, Missouri, United States
University of New Mexico Cancer Research and Treatment Center
🇺🇸Albuquerque, New Mexico, United States
Oncology Hematology West PC, Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Oncology Hematology Care, Inc.
🇺🇸Cincinnati, Ohio, United States
Columbia University
🇺🇸New York, New York, United States
St. Francis Cancer Center
🇺🇸Greenville, South Carolina, United States
Mary Crowley Cancer Research Center
🇺🇸Dallas, Texas, United States
Texas Oncology-Tyler
🇺🇸Tyler, Texas, United States
University of Texas, MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Northwest Cancer Specialists, P.C.
🇺🇸Vancouver, Washington, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Oncology and Hematology Associates of Southwest Virginia, Inc., Blue Ridge Cancer Care
🇺🇸Roanoke, Virginia, United States
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Korea Veterans Health Service
🇰🇷Seoul, Korea, Republic of
Texas Oncology-Austin Midtown
🇺🇸Austin, Texas, United States
Florida Cancer Affiliates
🇺🇸Ocala, Florida, United States
University of California, San Diego
🇺🇸San Diego, California, United States
Sarcoma Oncology Research Center
🇺🇸Santa Monica, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
CHI Health St Francis, Saint Francis Cancer Treatment Center
🇺🇸Grand Island, Nebraska, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States