Clinical trial NCT00855114: Everolimus in Treating Women With Breast Cancer That Can Be Removed by Surgery
Official title: A Phase II Trial of Short-Term Everolimus (RAD001) to Predict Response in Women With Operable Breast Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage II breast cancer
stage III breast cancer
stage IIIA breast cancer
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2009-03-04
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)
* 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)

Primary outcomes:
measure: Decrease of total choline in at least 30% of patients
timeFrame: Pre-Treatment Compared to Post-Treatment (Day 7)
Secondary outcomes:
measure: Identification of response to everolimus by activated mTOR signaling
timeFrame: Pre-Treatment Compared to Post-Surgery (Day 7)
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Children's Hospital - Fairview
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Douglas Yee, MD
role: PRINCIPAL_INVESTIGATOR
References: