Docetaxel Alone or in Combination With Vaccine to Treat Breast Cancer
This study will test whether giving a combination of a vaccine together with docetaxel is more effective against breast cancer than docetaxel alone. The Food and Drug Administration has approved docetaxel to treat many cancers, including breast cancer. The vaccine consists of three parts: 1) a "priming vaccine" called PANVAC[TM]-V, which is made from vaccinia virus; 2) a "boosting vaccine" called PANVAC[TM]-F, made from fowlpox virus; and 3) sargramostim, or GM-CSF, a protein that may help boost the immune system. Human genes are inserted into the vaccinia and fowlpox viruses to cause production of carcinoembryonic antigen (CEA) and mucin 1 (MUC-1)-two proteins that are often produced by cancer cells and can be used as a target for the immune system to attack the cancer. Another type of DNA is inserted to cause production of other proteins that enhance immune activity.
Patients 18 years of age or older with metastatic breast cancer (disease that has spread beyond the original site) and whose cancer produces CEA or MUC-1 protein may be eligible for this study. Patients must have antigen type HLA-A2. They may have received adjuvant docetaxel treatment at least 3 months before entering this study, prior hormonal therapy and up to three chemotherapy regimens. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram, and computerized tomography (CT) or magnetic resonance imaging scans.
Participants are randomly assigned to one of two treatment groups - docetaxel alone or docetaxel plus vaccine - as follows:
All patients receive docetaxel. The drug is infused through a vein over 30 to 60 minutes once a week for 3 consecutive weeks with 1 week off drug. Patients also take dexamethasone 12 hours and 1 hour before and 12 hours after the docetaxel to help prevent fluid retention (edema) that docetaxel may cause.
Docetaxel Plus Vaccine
Participants receive the priming vaccination followed by monthly boosting vaccinations, along with the weekly docetaxel therapy. With every vaccination, patients also receive an injection of sargramostim to increase the number of immune cells at the vaccination site. Sargramostim injections are given the day of vaccination and daily for the next 3 days. All vaccine and sargramostim doses are given as injections under the skin, usually in the thigh. Patients are observed in the clinic for 1 hour after each injection.
Patients have blood tests every four weeks to monitor drug side effects and before every vaccination to check blood counts. A bone scan or CT scan (or both) is done every 2 to 3 months to check the response to treatment.
Patients may continue receiving treatment as long as their disease does not worsen and they can tolerate the treatment without significant side effects. Patients assigned to receive docetaxel alone whose disease progresses after 3 months on the drug may choose to receive the vaccine or come off the study to receive other treatment options. Patients are monitored with yearly telephone calls for up to 15 years.
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Pilot Phase II Study of Docetaxel Alone or in Combination With PANVAC(Trademark)-V (Vaccinia) and PANVAC(Trademark)-F (Fowlpox) in Adults With Metastatic Breast Cancer|
- Progression-free survival. [ Designated as safety issue: No ]
- Overall survival. [ Designated as safety issue: No ]
- CD8+T cell responses. [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Estimated Study Completion Date:||May 2013|
|Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive vaccinia-CEA-MUC-1-TRICOM vaccine subcutaneously (SC) once and sargramostim (GM-CSF) SC once daily for 4 days in week -2. Patients also receive fowlpox-CEA-MUC-1-TRICOM vaccine SC once and GM-CSF SC once daily for 4 days in weeks 1, 5, and 9. Patients also receive docetaxel IV over 30 minutes once weekly in weeks 1-3, 5-7, and 9-11. After week 12, patients with no disease progression continue with docetaxel once weekly for 3 weeks followed by 1 week of rest and fowlpox-CEA-MUC-1-TRICOM vaccine plus GM-CSF every 4 weeks until disease progression.
given IVBiological: Familmarev
given subcutaneouslyBiological: Inalimarev
given subcutaneouslyBiological: Sargramostim
Experimental: Arm II
Patients receive docetaxel as in arm I. After week 12, patients with disease progression discontinue docetaxel and receive vaccinia-CEA-MUC-1-TRICOM vaccine, fowlpox-CEA-MUC-1-TRICOM vaccine, and GM-CSF as in arm I until further disease progression. Patients with no disease progression after week 12 continue with docetaxel as in arm I until disease progression.
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|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|United States, Texas|
|U.T.M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030-4096|
|Principal Investigator:||James L Gulley, M.D.||National Cancer Institute (NCI)|