Multipeptide Vaccine for Advanced Breast Cancer

Study Overview
=================
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: to test the safety of the combination of agents 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.

Official Title
-----------------
A Study of hTERT/Survivin Multi-peptide Vaccine With Daclizumab and Prevnar for Patients With Metastatic Breast Cancer

Conditions
-----------------
Breast Neoplasm, Breast Cancer, Cancer of the Breast, Carcinoma, Ductal

Intervention / Treatment
-----------------
* Biological: hTERT/Survivin Multi-Peptide Vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hTERT/Survivin Multi-Peptide Vaccine<br> | Biological: hTERT/Survivin Multi-Peptide Vaccine<br>* 100 mcg subcutaneous every 2 weeks four times, then monthly up to 28 vaccinations<br>* Other names: Telomerase;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  | Up to 30 days after the last vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunologic response |  | After 4th vaccination, then after every 3-4 vaccinations, and then every 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced breast cancer