Breast Cancer
Conditions
Keywords
stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, male breast cancer
Brief summary
RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells that express HER2/neu. Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop tumor cells from growing. It is not yet known whether vaccine therapy is more effective than GM-CSF in treating breast cancer. PURPOSE: This randomized phase II trial is studying vaccine therapy to see how well it works compared with GM-CSF in treating patients with breast cancer.
Detailed description
OBJECTIVES: * To determine if the GP2 peptide/GM-CSF vaccine reduces the recurrence rate in HLA-A2-positive, HER2/neu-positive, node-positive, or high-risk node-negative breast cancer patients randomized to receive the vaccine versus the immunoadjuvant, sargramostim (GM-CSF), alone. * To determine if the AE37 peptide/GM-CSF vaccine reduces the recurrence rate in HLA-A2-negative, HER2/neu-positive, node-positive or high-risk node-negative breast cancer patients randomized to receive the vaccine versus the immunoadjuvant, GM-CSF, alone. * To monitor the invitro and invivo immunologic responses to the vaccines and correlate these responses with the clinical outcomes. * To monitor for any unexpected toxicities with the vaccines. OUTLINE: This is a multicenter study. Patients are stratified according to nodal status. Patients are randomized to 1 of 4 treatment arms. * Arm I: HLA-A2-positive patients receive GP2 peptide/GM-CSF vaccine intradermally (ID) every 3-4 weeks for a total of up to 6 inoculations. * Arm II: HLA-A2-positive patients receive solely GM-CSF ID * Arm III: HLA-A2-negative patients receive AE37 peptide/GM-CSF vaccine ID every 3-4 weeks for a total of up to 6 inoculations. * Arm IV: HLA-A2-negative patients receive solely GM-CSF ID After completion of study therapy, patients are followed every 3 months for the first 24 months and then every 6 months for an additional 36 months. Booster inoculations are administered at 12, 18, 24, and 30 months from the date of patients' enrollment into the study. One booster inoculation is administered at each timepoint (+/- 2 weeks) and will be the same inoculation (vaccine or GM-CSF only) as what patients received during their regular inoculation series.
Interventions
BIOLOGICALGP2 peptide + GM-CSF vaccine
Given intradermally every 3-4 weeks for a total of up to 6 inoculations
BIOLOGICALGM-CSF (sargramostim)
GM-CSF given intradermally very 3-4 weeks for a total of up to 6 inoculations
BIOLOGICALAE37 + GM-CSF vaccine
Given intradermally every 3-4 weeks for a total of up to 6 inoculations
Sponsors
NuGenerex Immuno-Oncology
Norwell, Inc.
San Antonio Military Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Inclusion criteria: 1. Lymph node-positive breast cancer or high-risk lymph node-negative breast cancer. The latter is defined by any one of the following criteria: * T2 disease * Grade 3 disease * Lymphovascular invasion * Estrogen receptor- or progesterone receptor-negative disease * HER2/neu-expressing tumor (immunohistochemistry \[IHC\] 3+ and/or amplified fluorescence in situ hybridization \[FISH\] \>2.2, or N0 (i+)) 2. HER2/neu-expressing tumor (IHC 1-3+ and or positive FISH \>1.2) 3. Completion of primary standard of care breast cancer therapies (i.e., surgery, chemotherapy, immunotherapy and radiation therapy as appropriate per standard of care for patients' specific cancer) 4. Clinically cancer-free (no evidence of disease) 5. Patients may be enrolled between 1-6 months from completion of standard primary breast cancer therapies 6. Good performance status (as defined in
Exclusion criteria
) 7. Capable of informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease recurrence | Five years (from date of enrollment to the study through the end of the follow-up period) | The following will be compared: 1. disease recurrence rates between HLA-A2-negative patients receiving the AE37 + GM-CSF vaccine and HLA-A2-negative patients receiving GM-CSF alone 2. disease recurrence rates between HLA-A2-positive patients receiving the GP2 + GM-CSF vaccine and HLA-A2-positive patients receiving GM-CSF alone 3. disease recurrence rates between all four arms of the trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety | Local and systemic reactions to each inoculation will be monitored every six months during the regular inoculation series and the booster series. | Inoculations will be immediately halted if any serious adverse reactions occur which, when based upon appropriate judgment of the PI, are determined to jeopardize the patient or require medical or surgical intervention. Any death or grade 4 adverse drug experience found to be directly related to the experimental vaccine will result in suspension of patient enrollment to the study. |
| Immune Response | Immune response will be measured after every monthly inoculation in the regular inoculation series and after each inoculation in the booster series | Immune response will be measured by proliferation assays, dimer assays, and ELISPOT. Delayed type hypersensitivity reactions will be compared between the vaccinated group and GM-CSF-only group. |
Countries
Germany, Greece, United States
Outcome results
None listed