Everolimus in Treating Women With Breast Cancer That Can Be Removed by Surgery

University of Minnesota (UMN)

Status and phase

Withdrawn

Phase 2

Conditions

Breast Cancer

Treatments

Drug: everolimus

Procedure: therapeutic conventional surgery

Study type

Interventional

Funder types

Other

Identifiers

NCT00855114

0505M70026 (Other Identifier)

2005LS029

Details and patient eligibility

About

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.

Full 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.

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)
Creatinine ≤ 1.5 times ULN
Total bilirubin ≤ 1.5 times ULN
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception

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
- Severe infection
- Severe malnutrition
- Uncontrolled hypertension
- Unstable angina
- Ventricular arrhythmias
- Active ischemic heart disease
- Congestive heart failure
- Myocardial infarction within the past 6 months
- Chronic liver disease
- Renal disease
- Active upper gastrointestinal tract ulceration
Less than 4 weeks since prior investigational drug
Prior therapy with sirolimus or its analogues
Concurrent immunosuppressive therapy (e.g., steroids, cytotoxic agents, or concurrent radiotherapy)
Concurrent anticoagulation (i.e., coumadin)