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Multipeptide Vaccine for Advanced Breast Cancer

Sponsor
University of Pennsylvania (Other)
Overall Status
Completed
CT.gov ID
NCT00573495
Collaborator
(none)
11
Enrollment
1
Location
1
Arm
63
Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
  • Biological: hTERT/Survivin Multi-Peptide Vaccine
 Phase 1

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
11 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Study of hTERT/Survivin Multi-peptide Vaccine With Daclizumab and Prevnar for Patients With Metastatic Breast Cancer
Study Start Date :
Nov 1, 2007
Actual Primary Completion Date :
Jul 1, 2011
Actual Study Completion Date :
Feb 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: hTERT/Survivin Multi-Peptide Vaccine

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety [Up to 30 days after the last vaccination]

    Secondary Outcome Measures

    1. Immunologic response [After 4th vaccination, then after every 3-4 vaccinations, and then every 6 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Pennsylvania Medical Center Philadelphia Pennsylvania United States 19341

    Sponsors and Collaborators

    • University of Pennsylvania

    Investigators

    • Principal Investigator: Kevin Fox, MD, University of Pennsylvania

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Pennsylvania
    ClinicalTrials.gov Identifier:
    NCT00573495
    Other Study ID Numbers:
    • UPCC 08107
    First Posted:
    Dec 14, 2007
    Last Update Posted:
    Sep 29, 2016
    Last Verified:
    Sep 1, 2016
    Keywords provided by University of Pennsylvania
    Advanced breast cancer
    Additional relevant MeSH terms:
    Breast Neoplasms
    Carcinoma, Ductal
    BIRC5 protein, human

    Study Results

    No Results Posted as of Sep 29, 2016