Docetaxel Alone or in Combination With Vaccine to Treat Breast Cancer

Status:	Archived
Conditions:	Breast Cancer, Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	Any
Updated:	7/1/2011

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

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:

Docetaxel Alone

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.

Background:

Weekly docetaxel therapy is currently used as a standard treatment for patients with
metastatic breast cancer.

Although many patients initially respond to this form of therapy, the majority will
eventually develop disease progression and die from their disease.

We have explored the use of combining pox vector vaccines with docetaxel. In a recent
clinical trial, men with prostate cancer were given both the vaccine and docetaxel without
any significant toxicity and the docetaxel did not diminish immune responses to the vaccine.

Objectives:

To evaluate progression free survival comparing PANVAC + docetaxel vs. docetaxel alone in
patients with metastatic breast cancer.

To evaluate overall survival comparing PANVAC + docetaxel vs. docetaxel alone in patients
with metastatic breast cancer.

To evaluate in both arms CD8+ T cell responses directed against CEA and MUC-1 in HLA-A2, A3,
and A24 positive patients by interferon-gamma ELISPOT assay.

Eligibility:

Metastatic breast cancer (either male or female) with evidence of metastatic disease (must
have radiographic evidence of disease) and life expectancy of at least 4 months.

Patients may have received unlimited prior hormonal therapy or chemotherapy, but no prior
docetaxel for metastatic disease.

Hematological eligibility parameters within 16 days of starting therapy:

Granulocyte count greater than or equal to 1,500/mm(3), Platelet count greater than or equal
to 100,000/mm(3), Hgb greater than or equal to 8 Gm/dL.

Design:

We propose a randomized Phase II study evaluating the role of combining docetaxel with
PANVAC[TM]-V (recombinant vaccinia containing the genes encoding for CEA, MUC-1, LFA-3,
ICAM-1 and B7.1) and PANVAC[TM]-F (recombinant fowlpox containing the genes encoding for
CEA, MUC-1, LFA-3, ICAM-1 and B7.1) vs. docetaxel alone to determine if the addition of the
vaccine can prolong the time to disease progression as well as overall survival in patients
with metastatic breast cancer.

Patients randomized to docetaxel alone may receive sequential therapy with PANVAC[TM]-V and
PANVAC[TM]-F at time of disease progression.

In patients randomized to the concurrent therapy, PANVAC[TM]-V will be administered to
patients 3 weeks prior to the start of chemotherapy as the initial vaccine.

The immune responses to CEA and MUC-1 will then be boosted by administration of
PANVAC[TM]-F.

GM-CSF will be administered with each vaccine inoculation for four consecutive days only for
patients at the NCI.

We found this trial at

sites

University of Texas M.D. Anderson Cancer Center

1515 Holcombe Blvd
Houston, Texas 77030

713-792-2121