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

NCT02219711 | Completed Phase 1

• 1 other identifier: 516-001
• Study Type: interventional
• Target: 193
• Locations: 2 countries
• Sites: 43

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.

Conditions

Advanced Cancer

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; CBL; Sitravatinib

Outcome Measures

Primary Outcomes (3)

• 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

• Peak Plasma Concentration (Cmax) of MGCD516

  Up to 72 hours

Secondary Outcomes (3)

• 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

• Percent of patients having objective disease response to treatment

  Up to 1 year on treatment

Study Arms (1)

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

Drug: MGCD516

Interventions

MGCD516 DRUG

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

Also known as: Sitravatinib

MGCD516

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic or unresectable solid tumor malignancy
• Standard treatment is not available
• Adequate bone marrow and organ function

You may not qualify if:

• History of a significant cardiovascular illness
• Prolonged corrected QT (QTc) interval
• Left ventricular ejection fraction \< 40%
• Symptomatic or uncontrolled brain metastases
• Other active cancer

Sponsors & Collaborators

• Mirati Therapeutics Inc.: lead

Study Sites (43)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

University of California, San Diego

San Diego, California, 92093, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Innovative Clinical Research Institute

Whittier, California, 90602, United States

Location

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

Holy Cross Michael & Dianne Bienes Comprehensive Cancer Center

Fort Lauderdale, Florida, 33308, United States

Location

Florida Cancer Affiliates

Ocala, Florida, 34471, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Maryland Oncology Hematology,

Rockville, Maryland, 20850, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University Center for Advanced Medicine

St Louis, Missouri, 63110, United States

Location

CHI Health St Francis, Saint Francis Cancer Treatment Center

Grand Island, Nebraska, 68803, United States

Location

Oncology Hematology West PC, Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

University of New Mexico Cancer Research and Treatment Center

Albuquerque, New Mexico, 87102, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45242, United States

Location

Guthrie Clinical Research

Sayre, Pennsylvania, 18840, United States

Location

St. Francis Cancer Center

Greenville, South Carolina, 29607, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology-Austin Midtown

Austin, Texas, 78705, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75251, United States

Location

University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Oncology-Tyler

Tyler, Texas, 75702, United States

Location

The Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

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

Roanoke, Virginia, 24014, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Northwest Cancer Specialists, P.C.

Vancouver, Washington, 98684, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Chungbuk National University Hospital

Cheongju-si, South Korea

Location

Keimyung University Dongsan Hospital

Daegu, South Korea

Location

National Cancer Center

Goyang-si, South Korea

Location

Korea Veterans Health Service

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Related Publications (3)

• 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.

  PMID: 39513224 DERIVED

• 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.

  PMID: 39168901 DERIVED

• 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.

  PMID: 35767205 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Head and Neck Neoplasms; Carcinoma, Renal Cell; Prostatic Neoplasms

Interventions

sitravatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Genital Diseases; Prostatic Diseases

Study Officials

• Richard Chao, MD

  Mirati Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2014
• First Posted: August 19, 2014
• Study Start: August 1, 2014
• Primary Completion: April 27, 2022
• Study Completion: April 27, 2022
• Last Updated: March 6, 2023

Record last verified: 2023-03

Locations

KR (6); US (37)