Dose Escalation Followed by Study of RAD001 in Combination With Trastuzumab in HER2-Positive Metastatic Breast Cancer
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.
|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|
- 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 ]
- 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 ]
|Study Start Date:||April 2007|
|Estimated Study Completion Date:||December 2014|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
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
Given orally daily as long as participants cancer does not get worse or they experience harmful side effects.
Other Name: RAD001Drug: 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
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00458237
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Gerburg Wulf, MD, PhD||Beth Israel Deaconess Medical Center|