Clinical trial NCT00573495: Multipeptide Vaccine for Advanced Breast Cancer
Official title: A Study of hTERT/Survivin Multi-peptide Vaccine With Daclizumab and Prevnar for Patients With Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Neoplasm
Breast Cancer
Cancer of the Breast
Carcinoma, Ductal
Keywords: Advanced breast cancer
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2007-12-14
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety
timeFrame: Up to 30 days after the last vaccination
Secondary outcomes:
measure: Immunologic response
timeFrame: After 4th vaccination, then after every 3-4 vaccinations, and then every 6 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Kevin Fox, MD
role: PRINCIPAL_INVESTIGATOR
References: