Multipeptide Vaccine for Advanced Breast Cancer

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

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

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Breast Neoplasm; Carcinoma, Ductal; Cancer of the Breast
• Intervention / Treatment: Biological: hTERT/Survivin Multi-Peptide Vaccine

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 Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19341
      • University of Pennsylvania Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: December 12, 2007
• First Submitted That Met QC Criteria: December 12, 2007
• First Posted (Estimate): December 14, 2007

Study Record Updates

• Last Update Posted (Estimate): September 29, 2016
• Last Update Submitted That Met QC Criteria: September 27, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Advanced breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Carcinoma, Ductal; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Cysteine Proteinase Inhibitors; BIRC5 protein, human
• Other Study ID Numbers: UPCC 08107