RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole +/- goserelin (the latter for pre-menopausal women only) 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 hormone-sensitive metastatic 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 hormone-sensitive patients with metastatic breast cancer.
Name: IGF-1R inhibitor OSI-906
Description: Given orallyType: DrugLetrozole +/- goserelin, OSI-906, erlotinib (Arm II) Letrozole +/-goserelin, OSI-906 (Arm I )
Name: erlotinib hydrochloride
Description: Given orallyType: DrugLetrozole +/- goserelin, OSI-906, erlotinib (Arm II)
Name: goserelin
Description: Given subcutaneouslyType: DrugLetrozole +/- goserelin, OSI-906, erlotinib (Arm II) Letrozole +/-goserelin, OSI-906 (Arm I )
Name: letrozole
Description: Given orallyType: DrugLetrozole +/- goserelin, OSI-906, erlotinib (Arm II) Letrozole +/-goserelin, OSI-906 (Arm I )
Description: 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
Measure: Time to progression Time: from study entry to date of progressive diseaseDescription: The number of patients with worst-grade toxicity at each of five grades following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death
Measure: Safety profile of OSI-906 and letrozole +/ goserelin, with and without erlotinib Time: at 4 weeksDescription: Per RECIST criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions
Measure: Response Time: every 12 weeks to progressionDescription: Levels of the protein C-peptide and the hormone IGF-1 in the blood
Measure: Circulating C-peptide, IGF-1 Time: At baseline and on day 1 of each 28-day cycleDescription: The levels of these biomarkers will be measured in breast tumor tissue and compared and contrasted with patient's time to progression and molecular classification (luminal A vs. luminal B)
Measure: Correlation of IGF-IR, EGFR, HER2, Y1316 and Y1131 pIGF-1R, PTEN, S473 pAkt, pMAPK, S118 (MAPK site), and S167 (Akt and S6 site) pER expression with time to progression and molecular classification Time: On receipt of breast tissue: tissue block from prevous surgery or fresh tissue from current surgeryDescription: Breast tumor tissue will be examined for mutations in these genes.
Measure: Mutation analysis of PI3K (E542K, E545K, H1047R) Time: On receipt of breast tissue: tissue block from prevous surgery or fresh tissue from current surgeryAllocation: Randomized
Parallel Assignment
There are 3 SNPs
Mutation analysis of PI3K (E542K, E545K, H1047R). --- E542K ---
- 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 breast cancer OUTLINE: This is a multicenter study. --- E542K ---
Mutation analysis of PI3K (E542K, E545K, H1047R). --- E542K --- --- E545K ---
- 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 breast cancer OUTLINE: This is a multicenter study. --- E542K --- --- E545K ---
Mutation analysis of PI3K (E542K, E545K, H1047R). --- E542K --- --- E545K --- --- H1047R ---
- 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 breast cancer OUTLINE: This is a multicenter study. --- E542K --- --- E545K --- --- H1047R ---