Clinical trial NCT02219711: Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer
Official title: A Phase 1/1b Study of MGCD516 in Patients With Advanced Solid Tumor Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2014-08-19
Enrollment: 193
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Type of dose limiting adverse event
timeFrame: Up to 3 weeks on treatment
measure: Area under the plasma concentration versus time curve (AUC) of MGCD516
timeFrame: Up to 72 hours
measure: Peak Plasma Concentration (Cmax) of MGCD516
timeFrame: Up to 72 hours
Secondary outcomes:
measure: Kind of metabolites of MGCD516 in blood plasma
timeFrame: Up to 9 weeks on treatment
measure: Concentration of selected marker proteins in blood plasma
timeFrame: Up to 9 weeks on treatment
measure: Percent of patients having objective disease response to treatment
timeFrame: Up to 1 year on treatment
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Fort Lauderdale
country: United States
facility: Holy Cross Michael & Dianne Bienes Comprehensive Cancer Center
state: Florida
city: Ocala
country: United States
facility: Florida Cancer Affiliates
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Rockville
country: United States
facility: Maryland Oncology Hematology,
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University Center for Advanced Medicine
state: Missouri
city: Grand Island
country: United States
facility: CHI Health St Francis, Saint Francis Cancer Treatment Center
state: Nebraska
city: Omaha
country: United States
facility: Oncology Hematology West PC, Nebraska Cancer Specialists
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Research and Treatment Center
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Sayre
country: United States
facility: Guthrie Clinical Research
state: Pennsylvania
city: Greenville
country: United States
facility: St. Francis Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: Houston
country: United States
facility: University of Texas, MD Anderson Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology-Tyler
state: Texas
city: Salt Lake City
country: United States
facility: The Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Inc., Blue Ridge Cancer Care
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Korea Veterans Health Service
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
Study officials:
affiliation: Mirati Therapeutics Inc.
name: Richard Chao, MD
role: STUDY_DIRECTOR
References:
citation: 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.