Breast Cancer, Breast Neoplasm, Cancer of the Breast, Carcinoma, Ductal
Conditions
Keywords
Advanced breast cancer
Brief summary
This is a study on how to activate the immune system with a vaccine. The vaccine is made up of two proteins found in breast cancer: telomerase and survivin. The vaccine is given in combination with other drugs that may also have an effect on the immune system and attack the cancer. The goals of the study are: 1. to test the safety of the combination of agents 2. to find out what effects the treatment has on advanced breast cancer
Detailed description
Patients with advanced breast cancer may often fail standard of care treatments for metastatic disease. This research is studying a combinations of agents that impact the immune system. About \>85% of all human cancers, including breast cancer, express telomerase (hTERT) activity. Targeting hTERT immunologically may also minimize immune escape due to antigen loss because mutation or deletion of hTERT may be incompatible with sustained tumor growth. hTERT Multi-Peptide Vaccine is made up of 1540 hTERT peptide and cryptic peptides selected for low-affinity binding to HLA-A2 in order to increase the likelihood that the host immune system would ignore them, and then they have been modified by changing the first amino acid of the peptides to tyrosine in order to increase HLA - A2 affinity. The two heteroclitic peptides are R572Y (YLFFYRKSV) and D988Y (YLQVNSLQTV), which bind HLA-A2 with high avidity and elicit specific CTL (cytotoxic T lymphocyte) responses using healthy donor mononuclear cells in vitro. In addition, in mouse models, these peptide vaccines elicit lytic CTL responses which are protective against tumor challenges using a TERT-expressing murine tumor. Subjects will also be immunized with a peptide vaccine derived from survivin, an important anti-apoptotic protein which is overexpressed in a broad range of malignancies including breast cancer. Survivin may be an ideal and universal tumor antigen since it is overexpressed in a wide variety of cancers yet terminally differentiated adult cells do not express the protein. CMV derived CTL epitopes will be used as positive control peptides. Daclizumab is a humanized anti-human CD25 monoclonal antibody that binds specifically to CD25 expressing cells, including Treg cells, and inhibits its proliferation. Prevnar is designed to augment T-helper cell immunity.
Interventions
BIOLOGICALhTERT/Survivin Multi-Peptide Vaccine
100 mcg subcutaneous every 2 weeks four times, then monthly up to 28 vaccinations
Sponsors
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage IV breast cancer that has failed at least one conventional therapy for metastatic disease * HLA-A2 positive * Measurable or evaluable disease * ECOG performance status 0-1 * Negative contrast CT or MRI scan of the brain within 30 days of treatment * Negative pregnancy test within 14 days of treatment for women of childbearing potential
Exclusion criteria
* History of brain metastases within the last 4 years * The use of chemotherapy, radiation therapy, immunosuppressive drugs, systemic glucocorticoids, growth factors, or experimental therapy, and anti-coagulants within 14 days prior to treatment * Initiation of hormonal agent in the 30 days before treatment * Initiation of Herceptin in the 30 days prior to treatment. * History of bone marrow or stem cell transplantation * Pregnant or lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety | Up to 30 days after the last vaccination |
Secondary
| Measure | Time frame |
|---|---|
| Immunologic response | After 4th vaccination, then after every 3-4 vaccinations, and then every 6 months |
Countries
United States
Outcome results
None listed