Phase I/II Trial of IMC-A12 in Combination With Temsirolimus in Patients With Metastatic Breast Cancer
I. To establish the recommended dose level of cixutumumab and temsirolimus for the phase II
study in patients with metastatic breast cancer. (Phase I) II. To examine the safety profile
of this combination in patients with metastatic breast cancer. (Phase I) III. To assess the
anti-tumor activity (in terms of overall response rate) and toxicity profile of cixutumumab
in combination with temsirolimus in patients with metastatic breast cancer. (Phase II)
I. To estimate the progression-free survival (PFS) and overall survival distributions (as
well as the 6-month PFS rate).
II. To evaluate the in vivo mechanisms of action of temsirolimus in combination with
cixutumumab and to examine potential biomarker predictors of treatment response.
OUTLINE: This is a dose-escalation study of cixutumumab. Patients receive temsirolimus IV
over 30 minutes and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Courses repeat
every 28 days in the absence of disease progression or unacceptable toxicity.
Peripheral blood samples are collected periodically for circulating markers and mononuclear
cells. Samples are analyzed for pharmacodynamic assessments via western blot and proteomic
studies. If pre-existing tumor tissue is available, tissue is examined by
immunohistochemical staining for markers (e.g., pIRS-1, pIGF-IR, pMAPK, pAKT [S473], pS6,
PTEN, Stathmin). Fluorescence in situ hybridization is used to assess IGF-IR amplification.
Gene resequencing is performed to identify mutations of PIK3CA (exons 9 and 20), AKT1, and
other genes. Genes IGF-1, IGF-II, IGFBP-1, IGFBP-3, and others are analyzed by reverse
transcriptase-polymerase chain reaction.
After completion of study treatment, patients are followed up periodically for up to 2
(phase I) or 5 (phase II) years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended dose level for phase II testing (RPTD) (Phase I)
The RPTD is defined as the highest dose level at which at most one of 6 patients develops a dose limiting toxicity (DLT) during the first course of treatment. A two-stage Simon Phase II clinical trial design will be used to assess the toxicity profile of the combination of Temsirolimus and IMC-A12 at the recommended phase II dose in patients with metastatic breast cancer.
During first course
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|Bismarck Cancer Center||Bismarck, North Dakota 58501|
|Mid Dakota Clinic||Bismarck, North Dakota 58501|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Saint Alexius Medical Center||Bismarck, North Dakota 58501|
|Medcenter One Health Systems||Bismarck, North Dakota 58501|