A Phase II Trial of Endocrine Therapy in Combination With OSI-906 (an IGF-1R Inhibitor) With or Without Erlotinib (Tarceva, an EGFR Inhibitor) in Patients With Hormone-sensitive Metastatic Breast Cancer.
- To determine the antitumor activity of letrozole +/- goserelin (the latter for
pre-menopausal women only) in combination with IGF-1R inhibitor OSI-906 with or without
erlotinib hydrochloride, measured by time to progression, in patients with
hormone-sensitive metastatic breast cancer.
- To determine the safety of these regimens in these patients.
- To determine the response rate in patients treated with these regimens.
- To measure circulating C-peptide, IGF-1, and IGFBP-3 levels in patients treated with
- To correlate the expression of IGF-IR, EGFR, HER2, Y1316 and Y1131 pIGF-1R, PTEN, S473
pAkt, pMAPK, S118 (MAPK site), and S167 (Akt and S6 site) pER in formalin-fixed
paraffin blocks (FFPB) with clinical outcome and luminal A vs. luminal B subtypes of
- To correlate the mutational status of PI3K (E542K, E545K, H1047R) in DNA extracted from
FFPB or fresh biopsy with clinical outcome and luminal A vs. luminal B subtypes of
OUTLINE: This is a multicenter study. Stratification will be based on previous exposure to
endocrine therapy: (Arm I) no previous endocrine therapy or have completed adjuvant therapy
> 6 months prior to study enrollment; (Arm II) patients that had previous endocrine therapy
in the metastatic setting or had metastatic recurrence within 6 months of adjuvant endocrine
- Arm I: Patients receive oral letrozole once daily on days 1-28 +/- subcutaneous
goserelin* on day 1 and oral IGF-1R inhibitor OSI-906 twice daily on days 1-28.
Treatment repeats every 28 days in the absence of disease progression or unacceptable
- Arm II: Patients receive oral letrozole +/- subcutaneous goserelin* and IGF-1R
inhibitor OSI-906 as in arm I. Patients also receive oral erlotinib hydrochloride once
daily on days 1-28. Treatment repeats every 28 days in the absence of disease
progression or unacceptable toxicity.
NOTE: *Goserelin will only be given to premenopausal patients.
Tumor tissue samples from original diagnosis or from fresh biopsy tissue are collected for
biomarker analysis and other studies.
After completion of study therapy, patients are followed periodically.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Time to progression
Duration from study enrollment to date of progressive disease (PD) as measured by Response Evaluation in Solid Tumors (RECIST) criteria v. 1.1: measurable lesions: PD is > 20% increase in the sum of the longest diameter of target lesions or appearance of new lesions
from study entry to date of progressive disease
Ingrid Mayer, MD
Vanderbilt-Ingram Cancer Center
United States: Vanderbilt University Human Research Protection Program
VICC BRE 0977