Vaccine Therapy in Treating Patients With Stage III or Stage IV 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. Giving booster vaccinations may make a stronger immune response and kill more tumor cells. PURPOSE: This phase I trial is studying the side effects of vaccine therapy in treating patients with stage III or stage IV breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the safety of a vaccine comprising multiple synthetic breast cancer-associated peptides and a tetanus toxoid helper peptide emulsified in Montanide ISA-51 in patients with stage III or IV adenocarcinoma of the breast. Determine, preliminarily, the frequency of immune responses against the 9 class I MHC-restricted peptides in patients treated with the vaccine. Determine, preliminarily, the cytotoxic responses of T-cells to allogeneic breast cancer cells and autologous breast cancer cells (when available). OUTLINE: This is an open-label study. Patients receive peptide vaccine comprising 9 synthetic breast cancer peptides and tetanus toxoid helper peptide emulsified in Montanide ISA-51 subcutaneously and intradermally once daily on days 1, 8, 15, 36, 57, and 78 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 1 year. PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study.

Official Title
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Evaluation of the Safety and Immunogenicity of Vaccination With Multiple Synthetic Peptides in Participants With Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: synthetic breast cancer peptides-tetanus toxoid-Montanide ISA-51 vaccine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the breast Stage III or IV disease Primary or recurrent disease Invasive lobular carcinoma allowed HLA-A1, -A2, -A3, or -A31 positive Underwent and recovered from prior primary therapy Patients with no clinical or radiological evidence of disease who had a previous diagnosis of stage III or IV breast cancer must have undergone prior antineoplastic therapy including, but not limited to, surgery, chemotherapy, and radiotherapy within the past 36 months Must have at least one undissected axillary and/or inguinal lymph node basin No history of brain metastases Hormone receptor status Estrogen receptor-positive or -negative tumor PATIENT CHARACTERISTICS: ECOG performance status of 0 or 1 Body weight > 110 lbs (without clothes) Male or female Menopausal status not specified Absolute neutrophil count > 1000/mm^3 Platelet count > 100,000/mm^3 Hemoglobin > 9 g/dL Hemoglobin A1c < 7% AST and ALT ≤ 2.5 x upper limit of normal (ULN) Bilirubin ≤ 2.5 x ULN Alkaline phosphatase ≤ 2.5 x ULN Creatinine ≤ 1.5 x ULN HIV negative Hepatitis C negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known or suspected allergies to any component of the vaccine No active infection requiring antibiotics No New York Heart Association class III or IV heart disease No autoimmune disorders requiring cytotoxic or immunosuppressive therapy or autoimmune disorders with visceral involvement, except the following: Laboratory evidence of autoimmune disease (e.g., positive ANA titer) without symptoms Clinical evidence of vitiligo Other forms of depigmenting illness Mild arthritis requiring nonsteroidal antiinflammatory drugs No medical contraindication or potential problem that would preclude study participation PRIOR CONCURRENT THERAPY: More than 4 weeks since prior surgery More than 4 weeks since prior and no concurrent chemotherapy and radiotherapy More than 4 weeks since prior and no concurrent allergy desensitization injections More than 4 weeks since prior parenteral, oral, or inhaled corticosteroids No concurrent inhaled steroids (e.g., Advair® or triamcinolone acetonide) Prior or concurrent topical corticosteroids allowed More than 4 weeks since prior and no concurrent growth factors (e.g., epoetin alfa, darbepoetin alfa, or pegfilgrastim) More than 4 weeks since prior and no concurrent other investigational medication More than 4 weeks since prior and no concurrent other agents with putative immunomodulating activity except for non-steroidal anti-inflammatory agents Prior and concurrent hormonal therapy (e.g., tamoxifen, raloxifene, toremifene, fulvestrant, letrozole, anastrozole, or exemestane) allowed No prior vaccination with any synthetic peptides in this protocol Vaccines for infectious disease (e.g., influenza) allowed, provided they are administered ≥ 2 weeks prior to or ≥ 2 weeks after study vaccine Short term therapy for acute conditions not related to breast cancer allowed No concurrent illegal drugs

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stratum 1: Receiving Hormone Therapy<br>Patients treated with 9 peptide vaccine who received hormone therapy | Biological: synthetic breast cancer peptides-tetanus toxoid-Montanide ISA-51 vaccine<br> <br> |
| Experimental: Stratum 2: Not receiving hormone therapy<br>Patients receiving 9 peptide vaccine who did not receive hormone therapy | Biological: synthetic breast cancer peptides-tetanus toxoid-Montanide ISA-51 vaccine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants Who Experienced Dose-limiting Adverse Events | Safety of the 9-peptide mixture if fewer than 33% of patients experience a dose-limiting toxicity | 30 days post administration of last vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With T-cell Responses Against the Vaccine as Measured by Elispot Assay After 14 Day in Vitro Sensitization |  | Days 1-78 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIC breast cancer, stage IV breast cancer, male breast cancer, invasive lobular breast carcinoma, recurrent breast cancer, stage IIIA breast cancer, stage IIIB breast cancer