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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: everolimus; Procedure: therapeutic conventional 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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Children's Hospital - Fairview

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients Treated with Everolimus; Breast cancer patients treated with Everolimus by mouth, 5 mgs/day x 7 days, followed by surgery.	Drug: everolimus; 5 mg/day x 7 days by mouth; Other Names: RAD001; Afinitor(R); Procedure: therapeutic conventional surgery; Definitive excision of breast cancer tissue; Other Names: surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: Douglas Yee, MD, Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: March 3, 2009
• First Submitted That Met QC Criteria: March 3, 2009
• First Posted (Estimate): March 4, 2009

Study Record Updates

• Last Update Posted (Actual): December 2, 2017
• Last Update Submitted That Met QC Criteria: November 29, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage II breast cancer; stage III breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: 2005LS029; 0505M70026 (Other Identifier: IRB, University of Minnesota)