Clinical trial NCT00458237
Conditions: Breast Cancer
Keywords: HER2 positive metastatic breast cancer RAD001 Herceptin
Sponsor: Beth Israel Deaconess Medical Center
Start date: 2007-04-01; Completion date: 2010-04-01
Enrollment: 11 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
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.

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.
* Blood will be drawn on days 1, 2, 8, and 15 of the first cycle of treatment and then once at every 4 cycles for everolimus pharmacokinetics analysis.
* There is an optional tissue biopsy component to this study asking for 2 biopsies performed pre-treatment and after the cycle one.
* 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.

OBJECTIVES:

Primary

\- To assess the safety and tolerability of RAD001 in combination with trastuzumab in HER2-positive metastatic breast cancer

Secondary

* To evaluate the activity of RAD001 plus trastuzumab, as defined by objective response rate, in patients with progression on a trastuzumab-containing regimen
* To evaluate changes in signaling molecules in response to trastuzumab and RAD001 in circulating tumor cells and tumor tissue
* To evaluate the pharmacokinetics of RAD001 in combination with trastuzumab.

STATISTICAL DESIGN:

This Phase I study followed a standard 3+3 dose escalation design with two dose levels of everolimus in combination with trastuzumab to be evaluated. The DLT observation period was cycle one (first 21 days of treatment). There is a 20 patient expansion cohort treated at the MTD. The regimen would be considered promising if at least 2 objective responses are observed out of 20 treated patients. If the true but unknown response rate is 15% then the probability of observing at least 2 responses is 82% but if the true rate is 5% this probability reduces to 26%.

Arms: arm 1: Cycle duration is 21 days. Participants receive trastuzumab 6 mg/kg \[8 mg/kg loading dose\] IV once every three weeks and take everolimus 5 mg by mouth daily on days 1-21. Participants are treated until disease progression or unacceptable toxicity. arm 2: Cycle duration is 21 days. Participants receive trastuzumab 6 mg/kg \[8 mg/kg loading dose\] IV once every three weeks and take everolimus 10 mg by mouth daily on days 1-21. Participants are treated until disease progression or unacceptable toxicity. arm 3: Cycle duration is 21 days. Participants receive trastuzumab 6 mg/kg \[8 mg/kg loading dose\] IV once every three weeks and take everolimus at the MTD by mouth daily on days 1-21. Participants are treated until disease progression or unacceptable toxicity.
Interventions: intervention 1: Everolimus intervention 2: Trastuzumab
Intervention descriptions: intervention 1: Everolimus is being administered orally 7 days per week. intervention 2: Trastuzumab is being administered at a dose of 6 mg/kg intravenously once every 21 days.

Protocol documents: