Vaccine Therapy Plus Sargramostim and Chemotherapy in Treating Women With Stage II or Stage III Breast Cancer

OBJECTIVES:

• Compare the immunological effects of 2 different schedules of vaccinia-CEA-TRICOM vaccine, fowlpox-CEA-TRICOM vaccine, and sargramostim (GM-CSF) administered with standard adjuvant chemotherapy in women with high-risk stage II or III breast cancer.
• Compare the safety of these regimens in these patients.
• Determine the feasibility of obtaining determinations of CD4 response in patients treated with these regimens.
• Compare disease-free survival of patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

• Vaccinia-CEA-TRICOM: Beginning 2-3 weeks after surgery and before initiation of standard adjuvant chemotherapy, all patients receive vaccinia-CEA-TRICOM vaccine subcutaneously (SC) on day 1 and sargramostim (GM-CSF) SC on days 1-4 of week 1.
• Fowlpox-CEA-TRICOM: Patients are treated on 1 of the following schedules:

• Arm I: During chemotherapy, patients receive fowlpox-CEA-TRICOM vaccine SC on day 1 and GM-CSF SC on days 1-4 of weeks 2, 5, 8, 11, 14, 17, 20, and 23. After chemotherapy, patients receive additional vaccinations on weeks 26, 38, and 50.
• Arm II: Prior to chemotherapy, patients receive fowlpox-CEA-TRICOM vaccine SC on day 1 and GM-CSF SC on days 1-4 of week 2. After chemotherapy, patients receive additional vaccinations on weeks 26, 38, and 50.
• Chemotherapy: Patients receive doxorubicin IV over 5-7 minutes and cyclophosphamide IV over 30 minutes on day 1 of weeks 3, 6, 9, and 12. Patients then receive paclitaxel IV over 3 hours on day 1 of weeks 15, 18, 21, and 24. Treatment continues in the absence of disease progression (after at least 1 course of chemotherapy) or unacceptable toxicity.
• Radiotherapy: Patients undergo radiotherapy during weeks 26-32 in the absence of disease progression.

Patients with hormone-receptor positive tumors receive oral tamoxifen for 5 years beginning on approximately week 32.

Patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 28 (14 per treatment arm) patients will be accrued for this study within 18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast

• Stage II or III
• At least 4 positive lymph nodes
• No inflammatory ductal carcinoma
• No positive lymph nodes by immunohistochemistry only
• Carcinoembryonic antigen (CEA) expression, as indicated by 1 of the following:

• At least 30% of tumor stains for CEA on immunohistochemistry
• Elevated serum CEA (greater than 5 ng/mL) anytime during disease course
• Must be HLA-A2 positive
• Must have received prior vaccinia for smallpox immunization with 1 of the following as evidence:

• If age 25 and under, physician certification of prior vaccination
• If over age 25, patient recollection and vaccination-site scar
• Any age, detectable anti-vaccinia antibodies
• No metastases by CT scan of chest, abdomen, and pelvis and a bone scan
• Hormone receptor status:

• Estrogen receptor status and progesterone receptor status known

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status:

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT and SGPT no greater than 1.5 times ULN
• Hepatitis B and C negative

Renal

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min
• No proteinuria OR
• Protein less than 1,000 mg per 24-hour urine collection
• No hematuria
• No abnormal sediment

Cardiovascular

• LVEF at least 45% by echocardiogram or MUGA if either of the following are true:

• History of cardiac disease
• Received prior cardiotoxic chemotherapy

Immunologic

• No evidence of immunocompromised status
• No autoimmune disease such as any of the following:

• Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia
• Systemic lupus erythematosus
• Sjogren's syndrome
• Scleroderma
• Myasthenia gravis
• Goodpasture syndrome
• Addison's disease
• Hashimoto's thyroiditis
• Active Graves' disease
• No active or prior eczema or other eczematoid skin disorders
• No other acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
• HIV negative
• No active infection within the past 3 days
• No allergy to eggs
• No history of allergy or untoward reaction to prior vaccination with vaccinia virus

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other serious illness
• No other malignancy within the past 3 years except squamous cell or basal cell skin cancer
• No history of seizures, encephalitis, or multiple sclerosis
• No active inflammatory bowel disease
• Must be able to avoid close household contact with the following during and for 2 weeks after vaccinations:

• Persons with active or prior eczema or other eczematoid skin disorders
• Persons with any other acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
• Pregnant or nursing women
• Children under 5 years old
• Immunodeficient or immunosuppressed persons (by disease or therapy), including those with HIV infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• No prior doxorubicin, cyclophosphamide, or paclitaxel

Endocrine therapy

• No concurrent steroids except the following:

• Topical steroids
• Inhaled steroids for moderate asthma
• Dexamethasone prior to taxanes

Radiotherapy

• No prior radiotherapy to more than 50% of the lymph nodes

Surgery

• At least 2 weeks since prior surgery and recovered
• No prior splenectomy

Other

• No other concurrent anti-tumor therapies