Breast Cancer
Conditions
Keywords
recurrent breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, male breast cancer, invasive lobular breast carcinoma
Brief summary
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
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.
Interventions
BIOLOGICALsynthetic breast cancer peptides-tetanus toxoid-Montanide ISA-51 vaccine
Sponsors
National Cancer Institute (NCI)
University of Virginia
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Who Experienced Dose-limiting Adverse Events | 30 days post administration of last vaccine | Safety of the 9-peptide mixture if fewer than 33% of patients experience a dose-limiting toxicity |
Secondary
| Measure | 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 |
Countries
United States
Participant flow
Recruitment details
University of Virginia Dec 13, 2005 to May 6, 2008
Pre-assignment details
12 participants were registered to the study and 11 received vaccines. One participant was not compliant and did not receive vaccine.
Participants by arm
| Arm | Count |
|---|---|
| Stratum 1: Received Hormonal Therapy Participants received hormonal therapy | 6 |
| Stratum 2: Had Not Received Hormonal Therapy Participants had not received hormonal therapy | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Stratum 2: Had Not Received Hormonal Therapy | Stratum 1: Received Hormonal Therapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 6 Participants | 9 Participants |
| Age Continuous | 59.6 years STANDARD_DEVIATION 14.47 | 56.7 years STANDARD_DEVIATION 5.75 | 58.0 years STANDARD_DEVIATION 10.13 |
| Region of Enrollment United States | 5 participants | 6 participants | 11 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 1 / 5 |
| serious Total, serious adverse events | 1 / 6 | 0 / 5 |
Outcome results
Primary
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
Time frame: 30 days post administration of last vaccine
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum 1: Received Hormonal Therapy | The Number of Participants Who Experienced Dose-limiting Adverse Events | 1 participants |
| Stratum 2: Had Not Received Hormonal Therapy | The Number of Participants Who Experienced Dose-limiting Adverse Events | 0 participants |
Secondary
The Number of Participants With T-cell Responses Against the Vaccine as Measured by Elispot Assay After 14 Day in Vitro Sensitization
Time frame: Days 1-78
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum 1: Received Hormonal Therapy | The Number of Participants With T-cell Responses Against the Vaccine as Measured by Elispot Assay After 14 Day in Vitro Sensitization | 5 participants |
| Stratum 2: Had Not Received Hormonal Therapy | The Number of Participants With T-cell Responses Against the Vaccine as Measured by Elispot Assay After 14 Day in Vitro Sensitization | 3 participants |