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.
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
Last updated: 03/15/2012
NCT ID: NCT00640861
IRB Number:782-05
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