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Study of Combined Fulvestrant and RAD001 in Advanced/Metastatic Breast Cancer After Aromatase Inhibitor Failure (BRE-43)

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Suleiman Massarweh, University of Kentucky Identifier:
First received: December 7, 2007
Last updated: August 26, 2014
Last verified: August 2014

The primary objective of this study is to determine if estrogen receptor-targeted therapy with fulvestrant used in combination with RAD001 (Everolimus) is an effective and safe therapy for women with hormone receptor positive metastatic breast cancer after failure of aromatase inhibitor therapy.

Condition Intervention Phase
Breast Cancer
Drug: RAD001
Drug: Fulvestrant
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Combined Fulvestrant (Faslodex) and RAD001 (Everolimus) in Advanced/Metastatic Breast Cancer After Aromatase Inhibitor Failure

Resource links provided by NLM:

Further study details as provided by University of Kentucky:

Primary Outcome Measures:
  • Time to progression [ Time Frame: Duration of time start of treatment to time of documented progression or death ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rates [ Time Frame: Evaluated 60 days after therapy start ] [ Designated as safety issue: No ]
  • Clinical benefit rate [ Time Frame: Duration of response or stable disease for 24 weeks or more ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Study start through 1 month after treatment stop ] [ Designated as safety issue: Yes ]
  • Correlation between tumor biomarkers and treatment outcome [ Time Frame: Biopsy obtained at baseline & at day 28 ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: April 2008
Estimated Study Completion Date: June 2015
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Fulvestrant + RAD001
Drug: RAD001
RAD001 tablets, two-5 mg tablets a day
Other Name: Everolimus
Drug: Fulvestrant
intramuscular, 500 mg in two divided doses- one on each side- on day 1, then 250mg on day 14, then 250 mg on day 28 and every 4 weeks +/- 3 days thereafter
Other Name: Faslodex


Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No


All subjects must be female. Postmenopausal status, defined as any one of the following criteria: (a) Documented history of bilateral oophorectomy.

(b) Age 60 years or more. (c) Age 45 to 59 and satisfying one or more of the following criteria:

  1. Amenorrhea for at least 12 months and intact uterus.
  2. Amenorrhea for less than 12 months and a follicle stimulating hormone (FSH) concentration within postmenopausal range including:

    1. Patients who have had a hysterectomy.
    2. Patients who have received hormone replacement. Patients must have histologically confirmed invasive breast cancer. Metastatic or locally advanced disease. Patients must have estrogen receptor and/or progesterone receptor positive disease.

Measurable or evaluable disease. Failure of aromatase inhibitor therapy within the previous 6 months. Patients who received prior tamoxifen are eligible to enroll.

Prior aromatase inhibitor therapy or other endocrine therapy must be discontinued at least 1 week prior to enrollment and any toxicity from such therapy must have reverted to grade I or less at the time of enrollment.

Patients must not have received chemotherapy, radiation therapy, or had surgery within 4 weeks prior to enrollment and any toxicity from such therapy must have recovered to grade 1 or less prior to enrollment.

Patients must not have received either of the study medications previously. WHO performance status of 0, 1, or 2.

Adequate organ function defined as follows:

  1. Adequate renal function, defined by a serum creatinine within the upper limits of normal.
  2. Adequate liver function, defined by a bilirubin of < 1.5 the upper limit of normal (ULN) and AST, ALT of ≤ 2.5 times the ULN.
  3. Adequate bone marrow function, defined as an ANC ≥ 1.5 x 109/L, PLT >100,000/ul, Hb >9 gm/dl.
  4. INR <1.3.


Known severe hypersensitivity to RAD001 (or similar drugs) or any of the excipients of this product.

Premenopausal status. Other coexisting malignancies with the exception of basal cell carcinoma or cervical cancer in situ.

Patients with brain metastasis or leptomeningeal involvement. Patients with malignant pleural effusion or ascites only disease. Rapidly progressive visceral disease. WHO performance status of 3 or 4.

As judged by the investigator, uncontrolled intercurrent illness including, but not limited to:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris or significant cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • Severely impaired lung function such as severe COPD or interstitial lung disease, a known FEV1 of < 1.5 liters, or dyspnea of grade III or greater.
  • Uncontrolled diabetes as defined by a FBS of > 1.5 ULM.
  • Known liver disease such as cirrhosis or chronic hepatitis.
  • Known HIV positivity.
  • Known condition causing malabsorption. Chronic treatment with systemic steroids or other immunosuppressive agents. Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period.

Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the clinical trial.

Prior treatment with an mTOR inhibitor. Treatment with a non-approved or investigational drug within 30 days or 5 half-lives of the drug, whichever is greater, before Day 1 of study treatment.

In the opinion of the investigator, bleeding diathesis or anticoagulation therapy that would preclude intramuscular injections.

History of hypersensitivity to castor oil.

  Contacts and Locations
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Please refer to this study by its identifier: NCT00570921

United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
Sponsors and Collaborators
Suleiman Massarweh
Principal Investigator: Suleiman Massarweh, M.D. University of Kentucky
  More Information

Additional Information:
Responsible Party: Suleiman Massarweh, Clinical Faculty, Internal Medicine / Oncology, University of Kentucky Identifier: NCT00570921     History of Changes
Other Study ID Numbers: 07-BRE-43-NP
Study First Received: December 7, 2007
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Kentucky:
Breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Aromatase Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Enzyme Inhibitors
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on November 25, 2014