Vaccine and Chemotherapy for Previously Untreated Metastatic Breast Cancer

Summary

This study will evaluate the effectiveness of chemotherapy and a combination of vaccines to treat metastatic breast cancer (breast cancer that has spread beyond the breast) in patients whose cancer cells have a protein called carcinoembryonic antigen (CEA) on their surface. Patients who require surgery or radiation therapy, or both, will receive these treatments as well.

Patients 18 years of age and older with previously untreated metastatic breast cancer may be eligible for this study. Newly diagnosed patients may not have received prior chemotherapy. Patients previously diagnosed with local disease may have received chemotherapy or radiation therapy at least 18 months before entering the current study. Patients may have received hormonal therapy for stage IV disease. Candidates are screened with a medical history and physical examination, blood and urine tests, x-rays, heart and lung tests, and a test to determine the presence of CEA on their tumor cells.

Participants undergo the following procedures:

1. Central venous line: Under local or general anesthesia, an intravenous catheter (plastic tube) is inserted into a major vein in the chest. It is used to give chemotherapy and other medications and to withdraw blood samples.
2. Apheresis: Before beginning treatment and at various times before and after chemotherapy, patients undergo apheresis to collect white blood cells for later re-infusion at the time of immunizations and to evaluate the body's response to the vaccines. For this procedure, blood is collected through the central venous catheter and circulated through a machine that separates the white cells from the rest of the blood. The white cells are removed and frozen for later use. The rest of the blood is returned to the patient through the catheter.
3. First vaccine: Before starting chemotherapy, patients receive one subcutaneous (under the skin) injection of a vaccine called rV-CEA-Tricom, along with subcutaneous injections of granulocyte macrophage colony stimulating factor (GM-CSF) (Sargramostim), a drug that stimulates the bone marrow to release white blood cells and white cell precursors into the bloodstream.
4. Chemotherapy:

* Taxol (paclitaxel)/Cytoxan (cyclophosphamide): Patients receive three to five cycles of Taxol and Cytoxan. Taxol is given as a continuous 72-hour intravenous (intravenous (IV), through a vein) infusion and Cytoxan is given daily for 3 days, intravenously, over 1 hour. Cycles are 21 to 42 (usually 28) days. After each cycle, patients also receive growth colony stimulating factor (G-CSF) (a drug that helps boost white cells.

Conditions

• Breast Neoplasms
• Metastases, Neoplasm

Interventions

BIOLOGICAL

recombinant fowlpox-CEA(6D)/TRICOM vaccine

4 x 10\^8 pfu given monthly subcutaneously for three doses in the first series and three doses on each of the intermediate and late re-immunizations (total 9 doses).

BIOLOGICAL

recombinant vaccinia-CEA(6D)/TRICOM vaccine

rV-CEA (6D)/Tricom concomitantly with sargramostim (rGM-CSF). 1.2 x 10\^8 pfu x 1 dose subcutaneously.

BIOLOGICAL

filgrastim

5 mcg/kg/day subcutaneously

BIOLOGICAL

sargramostim

100 mcg daily for 4 consecutive days at the same site as the rF-CEA (6D)/Tricom vaccine. The first dose will be given with the vaccine.

DRUG

cyclophosphamide

First induction chemotherapy: 2700 mg/m\^2 per cycle (900 mg/m\^2 per day intravenous over 1 hour for 3 consecutive days, days 1-3). Second induction: 600 mg/m\^2 per cycle (600 mg/m\^2 intravenous over 1 hour day 1. Immune depleting chemotherapy: 2400 mg/m\^2 per cycle (600 mg/m\^2 per day intravenous over 1 hour for 4 consecutive days, days 1-4).

DRUG

doxorubicin hydrochloride

60 mg/m\^2 per cycle (60 mg/m\^2 slow intravenous push day 1).

DRUG

fludarabine phosphate

120 mg/m\^2 (30 mg/m\^2 per day intravenous over 30 minutes for 4 consecutive days (days 1-4)).

DRUG

paclitaxel

160 mg/m\^2 per cycle (53.3 mg/m\^2 per day by continuous intravenous infusion over 24 hours for 3 consecutive days 1-3).

DRUG

Mesna

Percent equals fraction of total daily cyclophosphamide dose. Initial: 20% of cyclophosphamide dose given intravenously (IV) mixed with cyclophosphamide. 3 hours post completion of cyclophosphamide: 20% intravenously (IV) or 40% by mouth (PO) 6 hours post completion of cyclophosphamide: 20% intravenously (IV) or 40% by mouth (PO) 9 hours post completion of cyclophosphamide: 20% intravenously (IV) or 40% by mouth (PO)

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Claude Sportes, M.D. · National Cancer Institute, National Institutes of Health

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2002-11-30

Primary Completion

2011-06-30

Completion

2011-06-30

Countries

• United States

Study Locations