Multi-institutional Phase II Study of IMC-A12, a Recombinant Human IgG1/λ Monoclonal Antibody Directed at the Type I Insulin-Like Growth Factor Receptor (IGF-1R), in Adrenocortical Carcinoma: A Randomized Trial Comparing the Activity of IMC-A12 With Mitotane Versus Mitotane Alone.
I. Compare the progression-free survival (PFS) rate in patients with recurrent, metastatic,
or primary unresectable adrenocortical carcinoma treated with mitotane with vs without
anti-IGF-1R recombinant monoclonal antibody IMC-A12 (IMC-A12).
I. Compare the response rates in these patients using Response Evaluation Criteria in Solid
Tumor (RECIST) criteria.
II. Compare the change in tumor size from baseline to 12 weeks in these patients.
III. Compare the overall trajectories in tumor growth in these patients.
I. Define predictive markers of response or insensitivity to IMC-A12. II. Define
pharmacodynamic markers of IMC-A12. III. Determine whether tumor expression of IGF-IR and
activation of downstream signaling in archival tumor tissue samples predict efficacy of
OUTLINE: This is a multicenter study that includes a single-arm safety evaluation phase
followed by a randomized phase. Initially, patients are enrolled in the safety evaluation
phase. If ≤ 6 of 20 patients experience a dose-limiting toxicity, then the study may proceed
to the randomized phase.
SAFETY EVALUATION PHASE: Patients receive oral mitotane once or twice daily and anti-IGF-1R
recombinant monoclonal antibody IMC-A12 IV over 1 hour once every 2 weeks in the absence of
disease progression or unacceptable toxicity.
RANDOMIZED PHASE: Patients are stratified according to participating center. Patients are
randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral mitotane once or twice daily in the absence of disease
progression or unacceptable toxicity. Patients with documented disease progression may cross
over and receive treatment on arm II.
ARM II: Patients receive mitotane as in arm I and anti-IGF-1R recombinant monoclonal
antibody IMC-A12 IV over 1 hour once every 2 weeks in the absence of disease progression or
Archival frozen tissue blocks, unstained tumor tissue slides from archival paraffin blocks,
plasma samples, and urine samples may be collected and stored for future correlative
After completion of study therapy, patients are followed up for 6 months.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
PFS based on RECIST
Progression-free survival rates will be estimated by the Kaplan-Meier method. The PFS curves will be compared using the logrank test. Additional analyses, adjusted for major prognostic variables will be performed by fitting Cox proportional hazards regression models. The goodness of fit of the Cox model will be assessed and the appropriate functional form for covariates will be determined through inspection of Schoenfeld and martingale residual plots.
Time from randomization to disease progression or death from any cause
University of Chicago Comprehensive Cancer Center
United States: Food and Drug Administration
|Central Illinois Hematology Oncology Center||Springfield, Illinois 62701|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center||Columbus, Ohio 43210-1240|
|Memorial Medical Center||Springfield, Illinois 62781|
|Ohio State University Medical Center||Columbus, Ohio 43210|
|Decatur Memorial Hospital||Decatur, Illinois 62526|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|University of Southern California||Los Angeles, California 90033|
|University of Michigan University Hospital||Ann Arbor, Michigan 48109|