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Randomized Phase II Trial of Trastuzumab or EVEROLIMUS in Hormone-refractory Metastatic Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Emory University
Genentech, Inc.
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Ruth O'Regan, Emory University Identifier:
First received: June 2, 2009
Last updated: June 3, 2014
Last verified: June 2014

The purpose of the study is to find out if trastuzumab or everolimus alone or in combination are effective in metastatic breast cancers that are no longer controlled by hormonal therapies.

Condition Intervention Phase
Breast Cancer
Drug: Trastuzumab (Herceptin)
Drug: Trastuzumab (Herceptin) plus Everolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Trastuzumab or EVEROLIMUS in Hormone-refractory Metastatic Breast Cancer

Resource links provided by NLM:

Further study details as provided by Emory University:

Primary Outcome Measures:
  • Response rate [ Time Frame: Every 6 to 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical benefit, progression-free survival [ Time Frame: Every 6 to 12 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 80
Study Start Date: May 2009
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Trastuzumab every 3 weeks.
Drug: Trastuzumab (Herceptin)
Trastuzumab 6mg/kg every 3 weeks (8mg/kg loading dose)
Other Names:
  • Trastuzumab
  • Herceptin
Experimental: B
Everolimus daily
Drug: Trastuzumab (Herceptin) plus Everolimus
Everolimus 10 mg daily
Other Names:
  • Trastuzumab
  • Herceptin
  • Everolimus

Detailed Description:

The purpose of this study is to investigate if trastuzumab or everolimus alone or in combination are effective for metastatic breast cancers that are no longer controlled with ( are resistant to) hormonal therapies, and express small to moderate amounts of HER2/neu. There is no standard of care for disease once it becomes resistant to hormonal therapy, and many patients are treated with chemotherapy. Trastuzumab alone or trastuzumab in combination with everolimus, have not been previously used to treat breast cancers than are resistant to hormonal therapies and have small to moderate amounts of HER2/neu. Everolimus alone has been demonstrated to improve outcome for patients with hormone-resistant metastatic breast cancer that is resident to hormonal agents.

In this study participants will be randomized 50:50 to receive trastuzumab alone or everolimus alone alone with the most recent hormonal agent they have taken. At the time of disease progression, patients randomized to receive trastuzumab will start everolimus, and patients randomized to everolimus will receive trastuzumab, so that all patients ultimately receive both agents. Trastuzumab is widely used to treat all stages of breast cancer, and is currently approved for the treatment of early and advanced breast cancer that have very high amounts of HER2/neu. Everolimus, when given with hormonal therapy, has been demonstrated to improve outcome for patients with hormone-resistant metastatic breast cancer. Patients will continue on the most recent hormonal therapy they received prior to entering this study.

It is hoped that trastuzumab alone, everolimus alone, or trastuzumab in combination with everolimus, may cause your tumor to stop growing or possibly to cause your tumor to shrink. This assessment will be based on measuring changes in the size of your tumor. You will be requested to have a biopsy of one of your metastatic areas prior to study entry to measure the amount of HER2/neu protein in your tumor.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Patients will be included in the study based on the following criteria:

  • Hormone-refractory metastatic breast cancer defined as disease progression within 6 months from starting most recent hormonal therapy
  • At least 2 prior endocrine therapies, including in the adjuvant setting. Patients must have had at least one hormonal agent in the metastatic setting
  • Candidate for hormonal therapy (ER and/or PR-positive at primary diagnosis and at metastatic diagnosis where tissue is available)
  • HER2/neu-negative breast cancer by standard criteria (FISH-negative and IHC <3+) at primary diagnosis
  • If biopsy of metastatic lesion is performed prior to study entry, HER2 expression by IHC must be 1+ or 2+.
  • Histologically confirmed, measurable disease
  • Life expectancy > 6 months
  • Age >18 years
  • ECOG performance status
  • Adequate bone marrow function as indicated by the following:

ANC >1500/uL Platelets ≥100,000/uL Hemoglobin >10 g/dL

  • Adequate renal function, as indicated by creatinine ≤1.5x upper limit of normal (ULN)
  • Adequate liver function, as indicated by bilirubin ≤1.5x ULN
  • INR ≤ 1.3 (or ≤ 3 on anticoagulants)
  • AST or ALT <2x ULN unless related to primary disease.
  • Signed informed consent
  • Adequate birth control
  • Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.

Exclusion Criteria:

Patients will be excluded from the study based on the following criteria:

  • Prior treatment with trastuzumab or other HER2-directed therapies or with an mTOR inhibitor within 12 months of study entry (when cancer was not definitely hormone refractory) (25)
  • HER2 0 or 3+ by IHC on pre-treatment biopsy of metastatic lesion (if performed)
  • Active infection
  • Uncontrolled central nervous system metastases
  • Pregnant or lactating women
  • Prior chemotherapy within the last 4 weeks
  • Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation).
  • Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
  • History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
  • Ejection fraction <50% or below the lower limit of the institutional normal range, whichever is lower
  • Hypersensitivity to trial medications
  • Emotional limitations
  • Prior treatment with any investigational drug within the preceding 4 weeks Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent
  • uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
  • liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  • A known history of HIV seropositivity
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Patients with an active, bleeding diathesis
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001)
  • Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
  • Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest
  • Taking any of the following agents:
  • chronic treatment with systemic steroids or another immunosuppressive agent
  • live vaccines
  • drugs or substances known to be inhibitors or inducers of the isoenzyme CYP3A
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00912340

Contact: Ruth O'Regan, MD 1-888-946-7447

United States, Georgia
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center of Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Caitlin1 C Meservey    312-695-1387   
Sponsors and Collaborators
Emory University
Genentech, Inc.
Novartis Pharmaceuticals
Principal Investigator: Ruth O'Regan, MD Emory University Winship Cancer Institute
  More Information

No publications provided

Responsible Party: Ruth O'Regan, Principal Investigator, Emory University Identifier: NCT00912340     History of Changes
Other Study ID Numbers: IRB00012495, WCI1524-08
Study First Received: June 2, 2009
Last Updated: June 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on November 27, 2014