Phase I/II Trial of Anti-IGF-IR Monoclonal Antibody IMC-A12 Plus mTOR Inhibitor Temsirolimus (CCI-779) in Metastatic Castration-Resistant Prostate Cancer (CRPC)
I. To confirm the safety and tolerability of IMC-A12 (cixutumumab) and temsirolimus using
the recommended phase II dose level for advanced solid tumors in chemo-naive patients with
metastatic castration-resistant prostate cancer and a rising prostate-specific antigen
(PSA). (Phase I) II. To confirm the safety and tolerability of IMC-A12 and temsirolimus
given on an every three weeks dosing schedule. (Phase I Extension) II. To determine the
tumor response rate and/or composite time to progression (cTTP) for chemotherapy-naive
patients with castration-resistant prostate cancer (CRPC) receiving the combination of
IMC-A12 and CCI-779 (temsirolimus). (Phase II)
I. To determine the maximal percent decrease in PSA from baseline. II. To determine the
change in PSA doubling time (PSADT). III. To determine the time to PSA progression and
6-month progression-free survival (PFS).
IV. To determine the rate of adverse events.
I. To evaluate changes in circulating tumor cell (CTC) numbers with time. II. To evaluate
IGF1R and androgen receptor (AR) in CTCs and correlate with response.
III. To evaluate profiling CTCs at the molecular level by polymerase chain reaction (PCR)
for prostate cancer-specific genes.
IV. To explore the association between clinical outcomes, administration of therapy, and
serial fludeoxyglucose F 18 (FDG)-positron emission tomography (PET) imaging.
V. To correlate fluorine F 18 FMDHT (18-FDHT)-PET imaging findings with outcome measures of
VI. To perform tumor biopsies and evaluate biomarkers that may correlate with active
feedback and tumor response to therapy, including anti-insulin receptor substrate 1 (IRS-1),
anti-IRS-2, phosphorylated (p) protein kinase B (Akt)(S473), p-ribosomal protein S6 kinase
(70/S6K), anti-phospho-AKT1 substrate 1 (proline-rich) (PRAS 40), and phosphatase and tensin
homolog gene (PTEN) status.
OUTLINE: This is a multicenter study.
Patients receive cixutumumab intravenously (IV) over 60-70 minutes and temsirolimus IV over
30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4 weeks.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Tumor response rate
Defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) and/or the proportion of patients who achieve a greater than 50% reduction in serum PSA compared to baseline.
Up to 4 weeks after completion of study treatment
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|University of Michigan University Hospital||Ann Arbor, Michigan 48109|