A Phase 2 Study of ARQ 197 in Patients With Previously-Treated Malignant Mesothelioma
I. To determine the objective response rate of patients with malignant mesothelioma who are
treated with ARQ 197 (tivantinib).
I. To determine the progression-free survival of patients with malignant mesothelioma who
are treated with ARQ 197.
II. To determine the toxicity experienced by patients with malignant mesothelioma who are
treated with ARQ 197.
III. To determine median and overall survival of patients with malignant mesothelioma who
are treated with ARQ 197.
I. To determine the frequency of mesenchymal-epithelial transition (MET) gene amplification
in malignant mesothelioma patient tumor samples, and to correlate the results with MET
II. To determine whether MET gene amplification results in increased sensitivity to ARQ 197
as observed by improved clinical outcomes (response rate [RR] and progression free survival
[PFS]) compared to those without MET gene over-expression/amplification.
III. To determine whether high baseline serum hepatocyte growth factor (HGF), as well as
changes in serum HGF during treatment at pre-defined early time points, correlate with
treatment efficacy and clinical outcome, as measured by response rate and progression-free
IV. To identify mutations by sequencing of specific areas of the MET gene in tumor samples
(semaphorin [SEMA], jumonji [JM] and tyrosine kinase domains).
V. To perform immunohistochemistry (IHC) of mesothelioma tumors for HGF, MET and
phosphorylated (p)-MET (pY1003 and pY1230/34/35).
VI. To assess serum HGF and serum soluble MET levels by enzyme linked immunosorbent assay
(ELISA) (R&D systems) pre-treatment, after 2 cycles and at disease progression.
Patients receive tivantinib orally (PO) twice daily (BID). Treatment continues in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 1 year.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective radiologic response rate (complete or partial response) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Up to 1 year
University of Chicago Comprehensive Cancer Center
United States: Food and Drug Administration
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|
|Ingalls Memorial Hospital||Harvey, Illinois 60426|
|City of Hope||Duarte, California 91010|
|Northwestern University||Chicago, Illinois 60611|
|Wayne State University||Detroit, Michigan 48202|
|Indiana University Medical Center||Indianapolis, Indiana 46202|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|Decatur Memorial Hospital||Decatur, Illinois 62526|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|University of Southern California||Los Angeles, California 90033|
|Penn State Milton S Hershey Medical Center||Hershey, Pennsylvania 17033|
|Evanston CCOP-NorthShore University HealthSystem||Evanston, Illinois 60201|
|Illinois CancerCare-Peoria||Peoria, Illinois 61615|
|Fort Wayne Medical Oncology and Hematology Inc - State Boulevard||Fort Wayne, Indiana 46845|
|Saint John's Mercy Medical Center||Saint Louis, Missouri 63141|
|University of Maryland Greenebaum Cancer Center||Baltimore, Maryland 21201|
|University of Michigan University Hospital||Ann Arbor, Michigan 48109|
|Southern Illinois University||Springfield, Illinois 62702|
|City of Hope- South Pasadena Cancer Center||South Pasadena, California 91030|