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

Sponsors and Collaborators:	Beth Israel Deaconess Medical Center Dana-Farber Cancer Institute Novartis Pharmaceuticals National Cancer Institute (NCI)
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00458237

Purpose

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: RAD001 Drug: Trastuzumab	Phase I Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Everolimus Trastuzumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety Study
Official Title:	A Brief Dose Escalation Followed by a Phase 2 Study of RAD001 in Combination With Trastuzumab in HER2-Positive Metastatic Breast Cancer

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 ]

Estimated Enrollment:	30
Study Start Date:	April 2007
Estimated Study Completion Date:	April 2009
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Intervention Details:

Given orally daily as long as participants cancer does not get worse or they experience harmful side effects.

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.

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.

Eligibility

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

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00458237

Contacts

Contact: Gerburg Wulf, MD, PhD

617-667-1910

gwulf@bidmc.harvard.edu

Locations

United States, Massachusetts
Beth Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02215
Contact: Jeanna Coviello 617-667-1940 jcoviell@bidmc.harvard.edu
Principal Investigator: Gerburg Wulf, MD, PhD
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Ian Krop, MD

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

Dana-Farber Cancer Institute

Novartis Pharmaceuticals

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Gerburg Wulf, MD, PhD

Beth Israel Deaconess Medical Center

More Information

No publications provided

Responsible Party:	Dana-Farber Cancer Institute ( Gerburg Wulf, MD )
Study ID Numbers:	06-124
Study First Received:	April 9, 2007
Last Updated:	April 27, 2009
ClinicalTrials.gov Identifier:	NCT00458237 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

HER2 positive
metastatic breast cancer
RAD001
Herceptin

Study placed in the following topic categories:

Everolimus
Immunologic Factors
Skin Diseases
Trastuzumab

Breast Neoplasms
Immunosuppressive Agents
Breast Diseases

Additional relevant MeSH terms:

Everolimus
Skin Diseases
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Breast Neoplasms
Immunosuppressive Agents

Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Trastuzumab
Breast Diseases

ClinicalTrials.gov processed this record on May 07, 2009