This study is for patients who are 18 years of age or older with stage II or III breast cancer. This study is experimental; it will review the safety and effectiveness of an experimental vaccine. This vaccine is given with the standard chemotherapy typically given for patients with early stage breast cancer. This treatment would start 2 to 3 weeks after surgery (lumpectomy or mastectomy). To be eligible for this study, you must have the following: stage II or III breast cancer with four or more positive lymph nodes, the tumor has the CEA protein, and your tissue type is HLA-A2. The experimental vaccine was made to specifically target the CEA protein which your tumor contains, as well as increase your immune system to kill your tumor. To target your tumor, scientists combined the CEA protein into a virus to create the vaccine. You will receive a priming vaccine one time with rV-CEA(6D)-TRICOM which is made from the vaccinia virus. You will receive several boosting vaccines with rF-CEA(6D)-TRICOM which is made from the fowlpox virus. Three molecules (TRICOM) were added inside the vaccine to help stimulate your immune system even more. These three costimulatory molecules are B7-1, ICAM-1, and LFA-3. These two vaccines and a third drug (Sargramostim) will all increase your immune system to kill your tumor.

Candidates will be screened with a medical history and physical examination; blood tests, including a test for HLA-A2 tissue type; urine tests, including a 24-hour urine collection and a pregnancy test in women of childbearing potential; and imaging studies, including X-rays, CT of the chest, abdomen and pelvis, bone scan, and MUGA scan or echocardiography, if recent studies are not available.

All patients will get standard chemotherapy with doxorubicin (Adriamycin® (Registered Trademark)), cyclophosphamide (Cytoxan® (Registered Trademark)), and paclitaxel (Taxol® (Registered Trademark)), in eight 21-day treatment cycles. The entire chemotherapy treatment will last for 6 months. Doxorubicin and cyclophosphamide will be given together by vein over 1 hour for the first four cycles. This will be followed by four cycles of paclitaxel. Paclitaxel is given by vein over 3 hours. All patients will receive vaccine treatment. However, patients will be randomly divided into two separate groups. Group A will receive vaccine before, during, and after chemotherapy; Group B will only receive vaccine before and after the chemotherapy, not during. The vaccines and Sargramostim will be injected under the skin of the thigh.

All patients (Group A and B) will start with the prime vaccine, then 2 weeks later, the boost vaccine is given. One week after this boost vaccine, chemotherapy will begin. Only patients in Group A will receive vaccine one week prior to each chemotherapy. The chemotherapy for all patients will end at 6 months. Starting 2 weeks after the chemotherapy, all patients (Group A and B) will get the boost vaccine. This vaccine will be given every 2 weeks to total three boost vaccines. Sargramostin is given daily for 4 days beginning with the day of each vaccine. At the end of 6 months, patients will also receive radiation. The plan for radiation therapy will be discussed with each patient. At this time, patients who had estrogen-receptor-positive tumors will take anti-estrogen medication, tamoxifen. Tamoxifen is a pill, taken by mouth daily for 5 years.

The study will last for about 1 year, may be shorter or longer depending on side effects and the immune response. After the first year, patients will have follow-up visits every 6 months for 5 years.

Patients will have blood tests before each vaccine and will also undergo lymphapheresis (a procedure for collecting immune cells called lymphocytes), on four occasions-before the first vaccination (day 0), after the first chemotherapy(week 3), after the last chemotherapy (week 26), and one month after the last chemotherapy(week 30). For this procedure, whole blood is collected through a needle in an arm vein, similar to donating blood. The blood circulates through a machine that separates it into its components, and the lymphocytes are removed. The rest of the blood is returned to the body, either through the same needle or through another needle in the other arm.

Condition	Treatment or Intervention	Phase
Breast Neoplasms	Drug: Recombinant Vaccinia-CEA(6D)-TRICOM  Drug: Recombinant Fowlpox-CEA(6D)-TRICOM	Phase II

Further Study Details: 

Expected Total Enrollment:  28

This trial will evaluate the immunologic effects of two vaccine arms priming with recombinant vaccinia virus that expresses the gene for the tumor associated antigen (TAA) CEA the gene for 3 costimulatory molecules B7.1, ICAM and LFA-3(TRICOM)[rV-CEA/TRICOM] followed by sequential vaccinations with recombinant fowlpox virus vaccinations containing the CEA gene and TRICOM (rF-CEA/Tricom). In arm A patients will receive vaccinations before and after as well as during the administration of an FDA approved chemotherapy regimen for adjuvant therapy in node positive breast cancer. Patients randomized to arm B will receive the vaccinations before and after chemotherapy, but not during the chemotherapy treatment. HLA-A2 patients with a PS level of 0-1 with CEA positive adenocarcinomas of the breast undergoing adjuvant chemotherapy following surgery with Stage 2 or 3 breast ca. with 4 or more + axillary lymph nodes will be eligible for the vaccine. The chemotherapy proposed in this study is a standard regimen and may be administered to the patient by a local oncologist or at the NIH Clinical Center. Patients may begin treatment 2-3 weeks post surgery. All vaccinations and blood draws for immunologic monitoring will be performed at the NIH Clinical Center on weeks 0 (day 1) 2, 3, 5, 8, 11, 14, 17, 20, 23, 26, 30, 38, 50 and 54. Patients will be followed for DFS (disease free survival) every 6 months after completion of the protocol until disease progression or for a total of 5 years at the NIH Clinical Center. Patients should continue follow up visits with their local oncologist on a 6-month basis.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Stage II-III, 4 or more + lymph nodes Adenocarcinomas of the Breast expressing CEA, excluding inflammatory ductal carcinoma. Patients must be HLA-A2+.
Patients must have a tumor which has been shown to express CEA by immunohistochemical techniques with at least 30% of the tumor staining for CEA, or have an elevated serum CEA greater than 5ng/ml at any point during their disease course.
Patients must be 18 years of age or older.
Patients must understand and sign informed consent that explains the neoplastic nature of his/her disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, potential risks and toxicities, and the voluntary nature of participation.
Patients must be ambulatory, with an ECOG performance status of 0 or 1.
Patients must have adequate organ function (within 16 days prior to study).:
Hematologic: WBC greater than or equal to 3,000/mm(3), ANC greater than or equal to 1500/mm(3), and platelet count greater than or equal to 100,000/mm(3);
Hepatic: bilirubin less than or equal to 1.5 x upper limit of normal, SGOT and SGPT less than or equal to 1.5 x upper limit of normal.
As entry criteria, a patient must have a CT scan of the chest/ abdomen/pelvis and a bone scan performed demonstrating no evidence of metastasis within 6 weeks prior to entry of study.
All patients must have received prior vaccinia (for smallpox immunization).
For patients less than or equal to 25 years of age, physician certification of prior smallpox immunization is required.
For patients greater than age 25, patient recollection and appropriate vaccination-site scar is sufficient evidence.
There must be no history of allergy or untoward reaction to prior vaccination with vaccinia virus.
Detectable anti-vaccinia antibodies will serve as sufficient proof of prior vaccination for patients of any age. Screening for anti-vaccinia antibodies will be performed only in patients who don't meet the above criteria. There must be no history of allergy or untoward reaction to prior vaccination with vaccinia virus.
Grade 0 proteinuria, Grade 0 hematuria, no abnormal sediment. Serum creatinine less than or equal to 1.5 mg/dl or a creatinine clearance greater than 60 ml/min. Patients may be eligible if the underlying cause of an abnormality is determined to be non-renal.
Because of the unknown effects of vaccines and dangers of chemotherapy on the fetus or neonate, patients of childbearing potential must agree to use adequate contraception while on study.
Patients should have fully recovered from surgery prior to beginning therapy. Patients may begin vaccinia at 2 weeks post surgery if the patient meets eligibility criteria.
Patients who have a history of cardiac disease or have had previous cardiotoxic chemotherapy will be required to undergo a baseline ECHO cardiogram or MUGA study. These patients must have an LV ejection fraction of greater than or equal to 45% to be eligible for study.
EXCLUSION CRITERIA:
Patients should have no evidence of being immunocompromised as defined by:
Diagnosis of altered immune function (HIV or Hepatitis B or C), or autoimmune disease (autoimmune neutropenia, thrombocytopenia, or hemolytic anemia; systemic lupus erythematosus, Sjogren syndrome, or scleroderma; myasthenia gravis; Goodpasture syndrome; Addison's disease, Hashimoto's thyroiditis, or active Graves' disease;
Prior splenectomy;
Concurrent steroid use, except topical steroids, inhaled steroids for moderate asthma, and decadron premedication prior to taxanes;
Other serious intercurrent illness. Patients with active infections are not eligible until the infection has cleared for at least three days;
History of other malignant process (excluding squamous cell or basal cell carcinoma of the skin), unless that previous tumor was treated with curative intent and the patient has been in remission for at least three years.
Patients can not have previously been treated with Doxorubicin, Cyclophosphamide, and Paclitaxel regimen used in this protocol. Patients may not have received XRT to greater than 50% of their lymph nodes.
Patients with a history of seizures, encephalitis, or multiple sclerosis are not eligible.
The recombinant vaccinia vaccine should not be administered if the following apply to either recipients or, for at least two weeks after vaccination, their close household contacts: persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne or other open rashes or wounds) until condition resolves; pregnant or nursing women; children under 5 years of age; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV infection. Close household contacts are those who share housing or have close physical contact.
Patients with known allergy to eggs are not eligible.
Women who are pregnant or nursing because of the unknown effects of vaccines and dangers of chemotherapy on the fetus or neonate.
Because of the potential for increased risk, patients with active inflammatory bowel disease will be excluded from CEA vaccine protocols.

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States

Study ID Numbers:  030005; 03-C-0005
Record last reviewed:  July 8, 2003
Last Updated:  September 3, 2003
Record first received:  October 3, 2002
ClinicalTrials.gov Identifier:  NCT00047398
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08