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

NCT ID: NCT02219711

Last Updated: 2023-03-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

193 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-08-31

Study Completion Date

2022-04-27

Brief Summary

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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

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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.

Conditions

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Advanced Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

MGCD516

Intervention Type DRUG

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

Interventions

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MGCD516

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

Intervention Type DRUG

Other Intervention Names

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Sitravatinib

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mirati Therapeutics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Richard Chao, MD

Role: STUDY_DIRECTOR

Mirati Therapeutics Inc.

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

University of California, San Diego

San Diego, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Sarcoma Oncology Research Center

Santa Monica, California, United States

Site Status

Innovative Clinical Research Institute

Whittier, California, United States

Site Status

Rocky Mountain Cancer Center

Denver, Colorado, United States

Site Status

Holy Cross Michael & Dianne Bienes Comprehensive Cancer Center

Fort Lauderdale, Florida, United States

Site Status

Florida Cancer Affiliates

Ocala, Florida, United States

Site Status

Florida Cancer Specialists

Sarasota, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Maryland Oncology Hematology,

Rockville, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Washington University Center for Advanced Medicine

St Louis, Missouri, United States

Site Status

CHI Health St Francis, Saint Francis Cancer Treatment Center

Grand Island, Nebraska, United States

Site Status

Oncology Hematology West PC, Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status

University of New Mexico Cancer Research and Treatment Center

Albuquerque, New Mexico, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Oncology Hematology Care, Inc.

Cincinnati, Ohio, United States

Site Status

Guthrie Clinical Research

Sayre, Pennsylvania, United States

Site Status

St. Francis Cancer Center

Greenville, South Carolina, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Texas Oncology-Austin Midtown

Austin, Texas, United States

Site Status

Mary Crowley Cancer Research Center

Dallas, Texas, United States

Site Status

University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Texas Oncology-Tyler

Tyler, Texas, United States

Site Status

The Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

Oncology and Hematology Associates of Southwest Virginia, Inc., Blue Ridge Cancer Care

Roanoke, Virginia, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Northwest Cancer Specialists, P.C.

Vancouver, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Chungbuk National University Hospital

Cheongju-si, , South Korea

Site Status

Keimyung University Dongsan Hospital

Daegu, , South Korea

Site Status

National Cancer Center

Goyang-si, , South Korea

Site Status

Korea Veterans Health Service

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Countries

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United States South Korea

References

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Bazhenova L, Kim DW, Cho BC, Goel S, Heist R, Werner TL, Eaton KD, Wang JS, Pant S, Adkins DR, Blakely CM, Yan X, Neuteboom S, Christensen JG, Chao R, Bauer T. Sitravatinib in patients with solid tumors selected by molecular alterations: results from a Phase Ib study. Future Oncol. 2024 Dec;20(39):3213-3227. doi: 10.1080/14796694.2024.2418285. Epub 2024 Nov 8.

Reference Type DERIVED
PMID: 39513224 (View on PubMed)

Pant S, Cho BC, Kyriakopoulos CE, Spira A, Tannir N, Werner TL, Yan X, Neuteboom S, Chao R, Goel S. Targeting multiple receptor tyrosine kinases with sitravatinib: A Phase 1b study in advanced renal cell carcinoma and castrate-resistant prostate cancer. Invest New Drugs. 2024 Oct;42(5):547-558. doi: 10.1007/s10637-024-01465-9. Epub 2024 Aug 21.

Reference Type DERIVED
PMID: 39168901 (View on PubMed)

Bauer T, Cho BC, Heist R, Bazhenova L, Werner T, Goel S, Kim DW, Adkins D, Carvajal RD, Alva A, Eaton K, Wang J, Liu Y, Yan X, Christensen J, Neuteboom S, Chao R, Pant S. First-in-human phase 1/1b study to evaluate sitravatinib in patients with advanced solid tumors. Invest New Drugs. 2022 Oct;40(5):990-1000. doi: 10.1007/s10637-022-01274-y. Epub 2022 Jun 29.

Reference Type DERIVED
PMID: 35767205 (View on PubMed)

Other Identifiers

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516-001

Identifier Type: -

Identifier Source: org_study_id

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