A Phase II Trial of Short-Term Everolimus (RAD001) to Predict Response in Women With Operable Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- everolimus
- Conditions
- Breast Cancer
- Sponsor
- Masonic Cancer Center, University of Minnesota
- Locations
- 1
- Primary Endpoint
- Decrease of total choline in at least 30% of patients
- Status
- Withdrawn
- Last Updated
- 8 years ago
Overview
Brief Summary
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase II trial is studying how well everolimus works in treating women with breast cancer that can be removed by surgery.
Detailed Description
OBJECTIVES: Primary * Determine whether the administration of everolimus results in a decrease of total choline, a surrogate marker of response, in at least 30% of women with resectable breast cancer. Secondary * Determine whether tumors with activated mTOR signaling, as measured by phosphorylation of 4E-BP1 and activity of cap dependent translational complex, will identify those women responsive to everolimus. OUTLINE: Patients receive oral everolimus once daily on days 1-7 in the absence of disease progression or unacceptable toxicity. Within 24 hours after completing everolimus, patients undergo surgery. Tumor tissue samples are collected at baseline and during surgery for the analysis of mTOR targets (i.e., 4E-BP1, p70S6 kinase phosphorylation), Ki67, cleaved caspase 3, and activity of cap dependent translational complex by immunohistochemical assays. Patients also undergo MRI/MRS before and after everolimus therapy for total choline and glucose levels measurement. After completion of study therapy, patients are followed for 30 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of invasive breast cancer
- •Resectable disease
- •Measurable disease, defined as a primary breast mass \> 2.0 cm by breast imaging or clinical exam
- •Planning to undergo surgical resection after neoadjuvant therapy
- •Menopausal status not specified
- •Eastern Clinical Oncology Group (ECOG) performance status 0-1
- •Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
- •Platelet count ≥ 100,000/mm\^3
- •Hemoglobin \> 9.0 g/dL
- •Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤ 2.5 times upper limit of normal (ULN)
Exclusion Criteria
- •Intracranial disease
- •Hormone receptor status not specified
- •Obese (\> 250 pounds)
- •Immunosuppression from any cause (e.g., known HIV infection)
- •History of severe asthma and/or allergies
- •History of severe claustrophobia
- •Ferromagnetic implants, history of shotgun wound and/or shrapnel, cardiac pacemakers, or other similar situations that would be contrary to strong magnetic force
- •Bleeding diathesis
- •Unstable systemic disease, including but not limited to, any of the following:
- •Uncontrolled diabetes
Arms & Interventions
Patients Treated with Everolimus
Breast cancer patients treated with Everolimus by mouth, 5 mgs/day x 7 days, followed by surgery.
Intervention: everolimus
Patients Treated with Everolimus
Breast cancer patients treated with Everolimus by mouth, 5 mgs/day x 7 days, followed by surgery.
Intervention: therapeutic conventional surgery
Outcomes
Primary Outcomes
Decrease of total choline in at least 30% of patients
Time Frame: Pre-Treatment Compared to Post-Treatment (Day 7)
Choline is measured by magnetic resonance imaging (MRI/MRS) scan.
Secondary Outcomes
- Identification of response to everolimus by activated mTOR signaling(Pre-Treatment Compared to Post-Surgery (Day 7))