A Randomized Phase II Trial of ARQ 197 (Tivantinib)/Cetuximab Versus Cetuximab in Patients With Recurrent/Metastatic Head and Neck Cancer
I. Response rate. We will compare the cetuximab/ARQ 197 (tivantinib) combination with
cetuximab single agent activity.
I. Continuous tumor shrinkage. II. Progression-free survival (PFS). III. Overall survival
(OS). IV. Endpoints I), II), and III) above, as well as response rates, will be assessed and
compared between treatment arms in the subgroup of patients with high c-MET expression
(anticipated to be ~84% of patients, and/or high c-MET copy number (anticipated >10% and
largely overlapping with MET IHC).
V. Single agent activity for ARQ 197 (tivantinib) in patients who have failed cetuximab.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1 and 15
and tivantinib orally (PO) twice daily (BID) on days 1-28.
ARM II: Patients receive cetuximab IV over 60-120 minutes on days 1 and 15. Patients who
fail cetuximab as a single agent may receive single agent tivantinib PO BID on days 1-28.
In both arms, courses repeat every 4 weeks in the absence of disease progression or
After completion of study treatment, patients are followed up for 8 weeks.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate (RECIST)
Response rates in the two arms will be compared using a continuity-corrected chi square test. A sample size of n=38 patients per arm will provide 80% power to detect a difference of 12% vs 35% between the cetuximab and combination treatment arms, using a one-sided test at the alpha = 0.10 significance level.
Up to 8 weeks after completion of study treatment
University of Chicago Comprehensive Cancer Center
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|University of Michigan Comprehensive Cancer Center||Ann Arbor, Michigan 48109-0752|
|Indiana University Cancer Center||Indianapolis, Indiana 46202-5265|
|University of Iowa Hospitals and Clinics||Iowa City, Iowa 52242|
|Northwestern Memorial Hospital||Chicago, Illinois 60611|
|Ingalls Memorial Hospital||Harvey, Illinois 60426|
|City of Hope Comprehensive Cancer Center||Duarte, California 91010|
|Mayo Clinic in Arizona||Scottsdale, Arizona 85259-5404|
|Mayo Clinic in Florida||Jacksonville, Florida 32224|
|Wayne State University||Detroit, Michigan 48202|
|USC Norris Comprehensive Cancer Center||Los Angeles, California 90089|
|UPMC Hillman Cancer Center||Pittsburgh, Pennsylvania 15232|
|Metro-Minnesota CCOP||St. Louis Park, Minnesota|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|Decatur Memorial Hospital||Decatur, Illinois 62526|
|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 Colorado Cancer Center - Anschutz Cancer Pavilion||Aurora, Colorado 80045|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital||Baltimore, Maryland 21231|
|University of Wisconsin Cancer Center Riverview||Wisconsin Rapids, Wisconsin 54494|
|Siteman Cancer Center at Washington University||Saint Louis, Missouri 63110|
|Southern Illinois University School of Medicine - Department of Surgery||Springfield, Illinois 62702|