Vaccine Therapy in Treating Patients With Previously Treated Stage II or Stage III Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. It is not yet known which vaccine is most effective in treating breast cancer. PURPOSE: This randomized clinical trial is studying the side effects of three different vaccine therapies and comparing the vaccines to see how well they work in treating patients with previously treated stage II or stage III breast cancer.

Detailed Description
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OBJECTIVES: Primary To determine the safety and immunization efficacy of MUC1 and HER-2/neu peptide vaccines combined with CpG oligodeoxynucleotide, sargramostim (GM-CSF), or both, as immune adjuvants suspended in Freund's incomplete adjuvant in patients with previously treated stage II or III adenocarcinoma of the breast. Secondary To describe the impact of immunization on clinical outcomes in patients with MUC1-positive breast cancer in terms of disease-free survival and overall survival. OUTLINE: Patients are stratified according to Her-2/neu status (positive vs negative). Patients are randomized to 1 of 3 treatment arms. Arm A: Patients receive a vaccine comprising incomplete Freund's adjuvant, MUC1 antigen vaccine, two Her-2/neu peptide-based vaccines, and sargramostim (GM-CSF) subcutaneously (SC) on day 1. Arm B: Patients receive a vaccine comprising incomplete Freund's adjuvant, MUC1 antigen vaccine, two Her-2/neu peptide-based vaccines (one of them different than in arm A), and CpG oligodeoxynucleotide SC on day 1. Arm C: Patients receive a vaccine comprising incomplete Freund's adjuvant, MUC1 antigen vaccine, two Her-2/neu peptide-based vaccines (one of them different than in arm A; the same as in arm B), GM-CSF, and CpG oligodeoxynucleotide SC on day 1. In all arms, treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who complete 6 courses of treatment without disease recurrence or a second primary or intolerable toxicity will go to the observation phase of the study for up to 2 years. Patients who develop recurrent disease during the observational phase will go to the event monitoring phase for up to 2 years. Blood samples are collected periodically. Blood samples and tissue samples from the patient's most recent surgery are used for correlative studies including immune responses to T helper and CTL epitopes by Elispot and tetramer analysis; and antigenic profiling by expression analysis of class I HLA antigens, MUC1, and HER-2 in tumor tissue. After completion of study treatment, patients are followed periodically until disease recurrence or for up to 2 years.

Official Title
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MUC1/HER-2/Neu Peptide Based Immunotherapeutic Vaccines for Breast Adenocarcinomas

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: CpG oligodeoxynucleotide
* Biological: HER-2/neu peptide vaccine
* Biological: MUC-1 peptide vaccine
* Biological: incomplete Freund's adjuvant
* Biological: sargramostim
* Other: immunoenzyme technique
* Other: immunologic technique


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the breast Clinical stage II or III disease No radiographic evidence of disease at the time of enrollment Has undergone surgery, adjuvant chemotherapy, and/or radiotherapy Completed standard first-line therapy only (including adjuvant therapy) for breast cancer within the past 3 months and currently with no evidence of disease Patients with stage I breast cancer with high-risk features are eligible provided 1 of the following criteria are met: HER2 over-expression or amplification Triple-negative (i.e., no expression of ER, PR, or over-expression of HER2 on routine immunohistochemical staining) . MUC1-positive breast cancer HLA-A2 positive Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified ECOG performance status 0-2 Hemoglobin ≥ 8.0 g/dL Platelet count ≥ 75,000/μL ANC ≥ 1,500/uL Creatinine ≤ 2 times upper limit of normal (ULN) AST ≤ 2 times ULN No uncontrolled infection No known HIV infection No other circumstances (e.g., concurrent use of systemic immunosuppressants or immunocompromising condition) that in the opinion of the physician would render the patient a poor candidate for this trial Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior invasive malignancies within the past 5 years (with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) PRIOR CONCURRENT THERAPY: See Disease Characteristics Fully recovered from acute, reversible effects of any prior breast cancer therapy No more than 3 years since prior surgery for primary breast cancer Concurrent anti-estrogen therapy is allowed No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation) No concurrent enrollment in any other study involving a pharmacologic agent (drugs, biologics, immunotherapy approaches, gene therapy) whether for symptom control or therapeutic intent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: CpG oligodeoxynucleotide|nan|
|Biological: HER-2/neu peptide vaccine|nan|
|Biological: MUC-1 peptide vaccine|nan|
|Biological: incomplete Freund's adjuvant|nan|
|Biological: sargramostim|nan|
|Other: immunoenzyme technique|nan|
|Other: immunologic technique|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of CD4+ T cells, CD8+ T cells, B cells, monocytes, and dendritic cells in a patient's peripheral blood sample as estimated by flow cytometry with a panel of monoclonal antibodies |  |  | 
| Frequency of peptide-specific IFN-gamma producing T cells and peptide-specific IL-5 producing T cells estimated by ELISPOT after in vitro stimulation with peptide-sensitized stimulator cells for MUC1 and HER-2 peptides |  |  | 
| Number and severity of hematologic and non-hematologic toxicities reported using the NCI-CTC version 3.0 criteria |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival, defined as the time from registration to the documentation of a first failure where a failure is the recurrence of breast cancer or a diagnosis of a second primary cancer |  |  | 
| Overall survival, defined as the time from registration to death due to any cause |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IA breast cancer, stage IB breast cancer, triple-negative breast cancer, HER2-positive breast cancer