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

Breast Cancer Clinical Trial

Official title:

A Phase II Trial of Short-Term Everolimus (RAD001) to Predict Response in Women With Operable Breast Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00855114
• Other study ID #: 2005LS029
• Secondary ID: 0505M70026
• Status: Withdrawn
• Phase: Phase 2
• First received: March 3, 2009
• Last updated: November 29, 2017
• Start date: July 2008
• Est. completion date: June 2009

Study information

• Verified date: November 2017
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• everolimus
5 mg/day x 7 days by mouth

Procedure:
• therapeutic conventional surgery
Definitive excision of breast cancer tissue

Locations

Country	Name	City	State
United States	University of Minnesota Children's Hospital - Fairview	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Decrease of total choline in at least 30% of patients	Choline is measured by magnetic resonance imaging (MRI/MRS) scan.	Pre-Treatment Compared to Post-Treatment (Day 7)
Secondary	Identification of response to everolimus by activated mTOR signaling	Two core biopsies will be obtained at the time of diagnostic biopsy. Waste tumor tissue obtained during surgery will be collected at the time of surgery. It will be stored under liquid nitrogen until they can be examined for activation of mTOR targets, specifically, 4E-BP1, p70S6 kinase phosphorylation, and activity of cap dependent translational complex.	Pre-Treatment Compared to Post-Surgery (Day 7)