RAD001 Plus Docetaxel in Patients With Metastatic Breast Cancer
- To assess the safety and tolerability and to find the maximum tolerated dose of the combination administration of RAD001 plus docetaxel when given to patients with metastatic breast cancer who are being considered for standard docetaxel treatment (phase I).
- To characterize the pharmacokinetics of RAD001 and docetaxel when co-administered (phase I).
- To determine the phosphorylation status of the components of the mTOR signaling pathway and the expression of modifiers of apoptosis in the primary breast tumors, in order to determine whether these markers can be used as predictors of sensitivity to the combination of RAD001 and docetaxel
- To determine the effect of the combination of RAD001 and docetaxel on the expression and phosphorylation of mTOR's targets in the accessible tumor tissue, in order to identify potential pharmacodynamics markers of response to this drug combination
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I, Open Label, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of the Combination RAD001 Plus Docetaxel in Patients With Metastatic Breast Cancer|
- Maximum Tolerated Dose (MTD) of combination of RAD001 plus Docetaxel [ Time Frame: 3 week cycles ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2005|
|Study Completion Date:||April 2012|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
Experimental: RAD001 + Docetaxel
RAD001 30 mg orally on Days 1 and 8. Docetaxel 40 mg/m^2 intravenous (IV) over 1 hour on Day 1. Dexamethasone 8 mg orally twice daily for 3 days, starting 24 hours prior to the administration of Docetaxel.
40 mg/m^2 IV over 1 hour on Day 1.
Other Name: TaxotereDrug: RAD001
30 mg orally on Days 1 and 8.Drug: Dexamethasone
8 mg orally twice daily for 3 days, starting 24 hours prior to the administration of Docetaxel.
Other Name: Decadron
Docetaxel is a drug approved for the treatment of metastatic breast cancer in patients who are either newly diagnosed or have failed earlier chemotherapy. RAD001 is an investigational drug that has shown to have anticancer properties. It also works by weakening the immune system. RAD001 works by blocking some of the steps required for cancer growth. The researcher hopes that RAD001 may increase the anticancer activity of docetaxel.
Before you can start treatment on this study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete medical history and physical exam. Blood (between 1-2 teaspoons) will be collected for routine tests. You will have scans (MRI or CT) to check on the status of your cancer as ordered by your primary physician. Women who are able to have children must have a negative blood pregnancy test. As part of the study researchers will also look at the tissue of your original cancer. Special stains will be done that will help find ways in which researchers can predict the response of your cancer to RAD001.
If you are found to be eligible to take part in this study, you will receive docetaxel by vein on Day 1 over one hour. RAD001 will be given by mouth on Days 1 and 8. RAD 001 will be given on an empty stomach or after a light meal. You will repeat this treatment every 21 days. Three (3 ) weeks equals 1 cycle.
Patients who participate on the first part of this study will be enrolled in groups of 3 at a time. The dose of RAD001 will be increased with each new group of patients. The dose of docetaxel will remain the same. The second part of the study will be using the highest dose of RAD001 and docetaxel that was found to be safe and effective during the first part of the study. (***Study did not progress to second part.***)
Dexamethasone will be given by mouth twice a day for 3 days, starting the day before you receive docetaxel. Dexamethasone helps decrease the risk of and control nausea, vomiting, and fluid retention.
Blood (between 1-2 teaspoons) will be drawn for routine tests at each visit. X-rays and scans (CT or MRI) will be done every 6 weeks to see if the tumor is responding to treatment.
After 6 cycles of the combination, docetaxel will be stopped and you will continue to take RAD001 alone. However, you may be able to take more than 6 cycles of the combination if you are not having any side effects and is found to be of benefit by your primary doctor.
Once you go off treatment, you will have a physical exam, including routine blood tests (1-2 teaspoons).
This is an investigational study. Docetaxel is approved by the FDA and commercially available for the treatment of breast cancer. RAD001 is authorized for use in research only. About 65 patients will take part in the study. All will be enrolled at M. D. Anderson.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00253318
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77230-1439|
|Principal Investigator:||Stacy Moulder, MD||M.D. Anderson Cancer Center|