Hormone Therapy and OSI-906 With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic Breast Cancer
Summary
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole or goserelin may fight breast cancer by lowering the amount of estrogen the body makes. OSI-906 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether hormone therapy and OSI-906 are more effective when given with or without erlotinib hydrochloride in treating breast cancer.
PURPOSE: This phase II trial is studying how well giving hormone therapy together with OSI-906 with or without erlotinib hydrochloride works in treating patients with metastatic breast cancer.
Description
OBJECTIVES:
Primary
- To determine the antitumor activity of letrozole or goserelin in combination with IGF-1R inhibitor OSI-906 with or without erlotinib hydrochloride, in terms of time to progression, in patients with hormone-sensitive metastatic breast cancer.
Secondary
- 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 these regimens.
- 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 different subtypes of breast cancer.
- To correlate the mutational status of PI3K (E542K, E545K, H1047R) in DNA extracted from FFPB or fresh biopsy with clinical outcome and different subtypes of breast cancer.
OUTLINE: This is a multicenter study. Patients are stratified according to prior endocrine therapy (yes vs no), and disease recurrence after > 6 months after completion of adjuvant therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral letrozole once daily on days 1-28 or goserelin* subcutaneously 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 toxicity.
- Arm II: Patients receive letrozole or 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 are collected for biomarker analysis and other studies.
After completion of study therapy, patients are followed up periodically.
Study Design
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Conditions
Breast Cancer
Intervention
IGF-1R inhibitor OSI-906, erlotinib hydrochloride, goserelin, letrozole
Status
Not yet recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01013506
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Goserelin
A synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE. Goserelin is used in treatments of malignant NEOPLASMS of the prostate, uterine fibromas, and metastatic breast cancer.
Inflammatory Breast Neoplasms
Metastatic breast cancer characterized by EDEMA and ERYTHEMA of the affected breast due to LYMPHATIC METASTASIS and eventual obstruction of LYMPHATIC VESSELS by the cancer cells.
Fadrozole
A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer.
Carcinoma, Lobular
A infiltrating (invasive) breast cancer, relatively uncommon, accounting for only 5%-10% of breast tumors in most series. It is often an area of ill-defined thickening in the breast, in contrast to the dominant lump characteristic of ductal carcinoma. It is typically composed of small cells in a linear arrangement with a tendency to grow around ducts and lobules. There is likelihood of axillary nodal involvement with metastasis to meningeal and serosal surfaces. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1205)
Mucin-1
Carbohydrate antigen elevated in patients with tumors of the breast, ovary, lung, and prostate as well as other disorders. The mucin is expressed normally by most glandular epithelia but shows particularly increased expression in the breast at lactation and in malignancy. It is thus an established serum marker for breast cancer.
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