Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Fulvestrant (Faslodex) Plus Everolimus in Post-Menopausal Patients With Hormone-Receptor Positive Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy
Post-menopausal women with hormone-receptor positive (HR+) metastatic breast cancer resistant to aromatase inhibitor (AI) therapy will be randomized to receive Fulvestrant (Faslodex) with Everolimus or Fulvestrant (Faslodex) with a placebo (no active ingredients). Fulvestrant has demonstrated activity when used as first, second, or third line endocrine therapy, making it an attractive therapy for combination with other agents. In addition, it is commonly reserved for use following disease progression on AI therapy. Everolimus is an orally administered drug that blocks a signaling pathway called "mTOR". "mTOR" acts as a regulator for many processes in the body, including cell growth. Blocking this pathway may have an effect on cell growth. The combination of a novel class of agents (mTOR inhibitors) and an established standard treatment for metastatic HR+ breast cancer may potentially increase the clinical benefit by targeting multiple different biological pathways.
- drug : Fulvestrant
- drug : Placebo (for Everolimus)
- drug : Everolimus
Phase: Phase 2
Ages Eligible For Study:
1. Signed informed consent. 2. ?18 years. 3. ECOG Performance Status 0 or 1. 4. Histologically or cytologically confirmed adenocarcinoma of the breast. 5. Stage IV disease or inoperable locally advanced disease. 6. ER and/or PR-positive disease. Tumors must be HER-2/neu negative or equivocal. 7. Aromatase Inhibitor (AI) resistant, defined as: - relapsed while receiving adjuvant therapy with an AI or, - progressive disease while receiving an AI for metastatic disease 8. Received one prior dose of fulvestrant within 28 days of randomization are eligible. - ?2 prior doses of fulvestrant are not eligible 9. Must be female and postmenopausal. 10. May have received ?1 prior systemic chemotherapy regimen for metastatic disease. 11. Adequate organ function: - WBC ?3.0 x 10?/L, ANC ?1.5 x 10?/L and platelet count ?100 x 10?/L - hemoglobin ?9 g/dL - serum bilirubin ?1.5 X ULN (Upper Limit of Normal) - AST or ALT ?2.5 X ULN (?5 x ULN in patients with liver metastases) - serum creatinine ?1.5 X ULN - serum albumin ?3 g/dL - fasting serum cholesterol ?300 mg/dL OR ?7.75 mmol/L AND fasting triglycerides ?2.5 x ULN. - PT with INR ?1.5 12. May have measurable disease, non-measurable disease, or both. 13. Basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix within the past five years treated with curative intent. History of prior malignancy are eligible if disease-free for >3 years.