A Randomized, Double-Blind, Placebo-Controlled Phase II Study of ARQ197 (Tivantinib) in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer
I. To determine progression-free survival (PFS) of men with minimally symptomatic or
asymptomatic metastatic, castrate-resistant, chemotherapy-naïve prostate cancer treated with
tivantinib (ARQ 197).
I. To determine the prostate-specific antigen (PSA) response rate at 12 weeks in men with
metastatic, castrate-resistant, chemotherapy-naïve prostate cancer treated with ARQ 197.
II. To determine the radiographic response rate at 12 weeks based on Response Evaluation
Criteria in Solid Tumors (RECIST) criteria on computed tomography (CT) scans and stability
of bone lesions on bone scan in castrate-resistant, chemotherapy-naïve prostate cancer
treated with ARQ 197.
III. To determine the proportion of patients who are progression-free at 12 weeks.
IV. To assess safety and tolerability in patients treated with ARQ 197 using the National
Institute of Cancer (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
grading of toxicities.
I. Evaluate markers of bone turnover. (Exploratory)
OUTLINE: This is a multicenter study. Patients are stratified according to prior abiraterone
or sipuleucel-T therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive tivantinib orally (PO) twice daily (BID) on days 1-28. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive placebo PO BID on days 1-28. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity. Patients with disease progression
may crossover to arm I.
Patients may undergo serum and urine sample collection at baseline and periodically during
treatment for biomarker studies.
After completion of study treatment, patients are followed up every 3 months for 6 months.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
PFS based on the RECIST criteria
The progression-free survival distributions between the two arms will be compared using log-rank tests. Progression-free survival curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model.
Time from study entry to the date of documented progression and/or death, assessed up to 6 months
J. Paul Monk
Ohio State University
United States: Food and Drug Administration
|Cleveland Clinic Foundation||Cleveland, Ohio 44195|
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Ingalls Memorial Hospital||Harvey, Illinois 60426|
|Northwestern University||Chicago, Illinois 60611|
|Case Western Reserve University||Cleveland, Ohio 44106|
|Ohio State University Medical Center||Columbus, Ohio 43210|
|Indiana University Medical Center||Indianapolis, Indiana 46202|
|Decatur Memorial Hospital||Decatur, Illinois 62526|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Lombardi Comprehensive Cancer Center at Georgetown University||Washington, District of Columbia 20057|
|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|
|Saint Joseph Medical Center||Towson, Maryland 21204|
|Southern Illinois University||Springfield, Illinois 62702|