Dose Escalation Followed by Study of RAD001 in Combination With Trastuzumab in HER2-Positive Metastatic Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2013 by Dana-Farber Cancer Institute.
Recruitment status was  Active, not recruiting
Dana-Farber Cancer Institute
Novartis Pharmaceuticals
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Gerburg Wulf, MD, PhD, Dana-Farber Cancer Institute Identifier:
First received: April 9, 2007
Last updated: November 5, 2013
Last verified: November 2013
The purpose of this research study is to determine the safety of RAD001 and the highest dose of this drug that can be given to people with HER2-positive metastatic breast cancer safely in combination with trastuzumab. RAD001 has been used in patients with severe rheumatoid arthritis, in recipients of solid-organ transplants, healthy volunteers and experiments with animals, and information from those other research studies suggest that this RAD001 may help to stop cancer cells from growing abnormally.

Condition Intervention Phase
Breast Cancer
Drug: Everolimus
Drug: Trastuzumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Brief Dose Escalation Followed by a Phase 2 Study of RAD001 in Combination With Trastuzumab in HER2-Positive Metastatic Breast Cancer

Resource links provided by NLM:

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • To assess the safety and tolerability of RAD001 in combination with trastuzumab in HER2-positive metastatic breast cancer. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the activity of RAD001 plus trastuzumab, as defined by objective response rate, in patients with progression on a trastuzumab-containing regimen [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • to evaluate changes in signaling molecules in response to trastuzumab and RAD001 in circulating tumor cells and tumor tissue [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • to evaluate the pharmacokinetics of RAD001 in combination with trastuzumab. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: April 2007
Estimated Study Completion Date: December 2014
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus and Trastuzumab
This is an early-phase clinical study that examines the safety and feasibility of the combination of standard dose Trastuzumab with escalating doses of Everolimus for the treatment of Her2-positive, metastatic breast cancer
Drug: Everolimus
Given orally daily as long as participants cancer does not get worse or they experience harmful side effects.
Other Name: RAD001
Drug: Trastuzumab
Infusion once every 3 weeks (3 weeks equals one cycle) for as long as participants cancer does not get worse or they experience harmful side effects.
Other Name: Herceptin

Detailed Description:
  • Since we are looking for the dose of RAD001 that can be given safely in combination with trastuzumab, not everyone will receive the same amount of RAD001. Small groups of participants will be enrolled at a certain dose of RAD001 and if they tolerate the medications well, the next small group will receive a higher dose. This will continue until the optimal dose of RAD001 that can be given in combination with trastuzumab is found.
  • Participants will receive trastuzumab through an IV once every three weeks and will take RAD001 by mouth daily. This three week regimen is called a cycle. A study diary will be provided to record the doses of RAD001 that the participant takes.
  • During all treatment cycles, participants will have a physical exam and be asked questions about their general health including specific questions about any side effects they may be experiencing. They will need to come to the clinic weekly during the first cycle, then every cycle for the remainder of the study.
  • Every 9 weeks (3 cycles) the tumor will be reassessed with a MUGA or MRI scan. After the first 3 cycles a MUGA scan or echocardiogram will be repeated. It there are abnormalities, the test will be repeated more often.
  • Blood work will be drawn on days 1, 2, 8, and 15 of the first cycle of treatment and then once at every restaging (every 4 cycles).
  • There is an optional tissue biopsy component to this study. We will ask permission to perform 2 biopsies. The first biopsy will be performed before the participant starts receiving the study treatment and the second will be performed after the first cycle of treatment.
  • We will keep track of the participants medical condition for the next three years by calling them on the telephone twice a year to see how they are doing.
  • Participants may remain on the study treatment as long as their cancer does not progress and they are not experiencing any harmful side effects from the treatment.

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

Inclusion Criteria:

  • Histologically or cytologically confirmed invasive breast cancer, with stage IV disease
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as greater than or equal to 20mm with conventional techniques or as greater than or equal to 10mm with spiral CT scan.
  • Primary tumor or metastasis must overexpress HER2
  • Patient must have received 1-2 prior chemotherapeutic regiments for metastatic breast cancer and must have been off treatment for at least three weeks.
  • Patient must have received and progressed on at least 1 prior trastuzumab-containing regimen, but not more than 2, in the metastatic setting.
  • Patients may have received prior radiation therapy
  • Patients may have received hormonal therapy in the adjuvant or metastatic setting
  • 18 years of age or older
  • Life expectancy of greater than 6 months
  • Normal organ and marrow function as defined in the protocol
  • Left ventricular ejection fraction (LVEF) greater than or equal to the institutional lower limit of normal

Exclusion Criteria:

  • Treatment with any investigational drug within 4 weeks
  • Long-term treatment, over 3 months, with a systemic steroid or another immunosuppressive agent
  • Other malignancies within the past 3 years, except for adequately treated carcinoma of teh cervix or basal-or squamous-cell carcinoma of the skin
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
  • An active, bleeding diathesis or an oral anti-vitamin K medication
  • Prior treatment with an mTOR inhibitor
  • History of non-compliance with medical regimens
  • Unwillingness or inability to comply with the protocol
  • Major surgery within 2 weeks before study entry
  • Patients with active brain metastases or leptomeningeal carcinomatosis
  • Patients who have experienced grade 1 or grade 2 hypersensitivity reactions to prior trastuzumab therapy are eligible ONLY IF these reactions did not prevent further administration
  • Severe and/or uncontrolled intercurrent medical condition, psychiatric illness or a social situation that could limit their ability to comply with the study requirements.
  • Pregnant or breast-feeding women
  • HIV positive patients
  • Known hypersensitivity to RAD001 (everolimus) or other rapamycins
  Contacts and Locations
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Please refer to this study by its identifier: NCT00458237

United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute
Novartis Pharmaceuticals
National Cancer Institute (NCI)
Principal Investigator: Gerburg Wulf, MD, PhD Beth Israel Deaconess Medical Center
  More Information

Responsible Party: Gerburg Wulf, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute Identifier: NCT00458237     History of Changes
Other Study ID Numbers: 06-124 
Study First Received: April 9, 2007
Last Updated: November 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
HER2 positive
metastatic 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 February 04, 2016