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

Advanced Cancer Clinical Trial

Official title:

A Phase 1/1b Study of MGCD516 in Patients With Advanced Solid Tumor Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02219711
• Other study ID #: 516-001
• Status: Completed
• Phase: Phase 1
• Start date: August 2014
• Est. completion date: April 27, 2022

Study information

• Verified date: March 2023
• Source: Mirati Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 193
• Est. completion date: April 27, 2022
• Est. primary completion date: April 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Cancer
• Neoplasms

Intervention

Drug:
• MGCD516
MGCD516 is a small molecule inhibitor of several closely related receptor tyrosine kinases. MGCD516 capsules will be taken with water.

Locations

Country	Name	City	State
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Korea Veterans Health Service	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
United States	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico
United States	University of Michigan	Ann Arbor	Michigan
United States	Texas Oncology-Austin Midtown	Austin	Texas
United States	University of Alabama	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Holy Cross Michael & Dianne Bienes Comprehensive Cancer Center	Fort Lauderdale	Florida
United States	CHI Health St Francis, Saint Francis Cancer Treatment Center	Grand Island	Nebraska
United States	St. Francis Cancer Center	Greenville	South Carolina
United States	University of Texas, MD Anderson Cancer Center	Houston	Texas
United States	University of Wisconsin	Madison	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University	New York	New York
United States	Florida Cancer Affiliates	Ocala	Florida
United States	Oncology Hematology West PC, Nebraska Cancer Specialists	Omaha	Nebraska
United States	Oncology and Hematology Associates of Southwest Virginia, Inc., Blue Ridge Cancer Care	Roanoke	Virginia
United States	Maryland Oncology Hematology,	Rockville	Maryland
United States	Washington University Center for Advanced Medicine	Saint Louis	Missouri
United States	The Huntsman Cancer Institute	Salt Lake City	Utah
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	Florida Cancer Specialists	Sarasota	Florida
United States	Guthrie Clinical Research	Sayre	Pennsylvania
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Texas Oncology-Tyler	Tyler	Texas
United States	Northwest Cancer Specialists, P.C.	Vancouver	Washington
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Type of dose limiting adverse event		Up to 3 weeks on treatment
Primary	Area under the plasma concentration versus time curve (AUC) of MGCD516		Up to 72 hours
Primary	Peak Plasma Concentration (Cmax) of MGCD516		Up to 72 hours
Secondary	Kind of metabolites of MGCD516 in blood plasma		Up to 9 weeks on treatment
Secondary	Concentration of selected marker proteins in blood plasma	Proteins include VEGF A, soluble VEGF-R2 and soluble MET	Up to 9 weeks on treatment
Secondary	Percent of patients having objective disease response to treatment	Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	Up to 1 year on treatment