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.
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.
Brief Title
Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Advanced Cancer
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
* 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
Inclusion Criteria
Inclusion Criteria:
* Metastatic or unresectable solid tumor malignancy
* Standard treatment is not available
* Adequate bone marrow and organ function
* Metastatic or unresectable solid tumor malignancy
* Standard treatment is not available
* Adequate bone marrow and organ function
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02219711
Org Class
Industry
Org Full Name
Mirati Therapeutics Inc.
Org Study Id
516-001
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1/1b Study of MGCD516 in Patients With Advanced Solid Tumor Malignancies
Primary Outcomes
Outcome Measure
Type of dose limiting adverse event
Outcome Time Frame
Up to 3 weeks on treatment
Outcome Measure
Area under the plasma concentration versus time curve (AUC) of MGCD516
Outcome Time Frame
Up to 72 hours
Outcome Measure
Peak Plasma Concentration (Cmax) of MGCD516
Outcome Time Frame
Up to 72 hours
Secondary Outcomes
Outcome Time Frame
Up to 9 weeks on treatment
Outcome Measure
Kind of metabolites of MGCD516 in blood plasma
Outcome Description
Proteins include VEGF A, soluble VEGF-R2 and soluble MET
Outcome Time Frame
Up to 9 weeks on treatment
Outcome Measure
Concentration of selected marker proteins in blood plasma
Outcome Description
Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Outcome Time Frame
Up to 1 year on treatment
Outcome Measure
Percent of patients having objective disease response to treatment
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sanjay Goel
Investigator Email
sgoel@montefiore.org
Investigator Phone
718-405-8404
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Endocrine System Cancers --- HEAD AND NECK NEOPLASMS
Prostate Cancer --- PROSTATIC NEOPLASMS
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
Endocrine System Cancers --- ADENOCARCINOMA
Cancer --- CARCINOMA
Lung & Chest Cancers --- NEOPLASMS, GLANDULAR AND EPITHELIAL
Prostate Cancer --- UROGENITAL NEOPLASMS
Kidney & Urinary Tract --- KIDNEY DISEASES
Kidney & Urinary Tract --- UROLOGIC DISEASES
Prostate Cancer --- GENITAL NEOPLASMS, MALE
Prostate Cancer --- PROSTATIC DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
HEAD AND NECK NEOPLASMS
CARCINOMA, RENAL CELL
PROSTATIC NEOPLASMS
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
SITRAVATINIB