Multipeptide Vaccine for Advanced Breast Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00573495
• Other study ID #: UPCC 08107
• Status: Completed
• Phase: Phase 1
• First received: December 12, 2007
• Last updated: September 27, 2016
• Start date: November 2007
• Est. completion date: February 2013

Study information

• Verified date: September 2016
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: February 2013
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasm
• Breast Neoplasms
• Cancer of the Breast
• Carcinoma, Ductal

Intervention

Biological:
• hTERT/Survivin Multi-Peptide Vaccine
100 mcg subcutaneous every 2 weeks four times, then monthly up to 28 vaccinations

Locations

Country	Name	City	State
United States	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety		Up to 30 days after the last vaccination	Yes
Secondary	Immunologic response		After 4th vaccination, then after every 3-4 vaccinations, and then every 6 months	No