Safety and Efficacy Study of HER2/Neu (E75) Vaccine in Breast Cancer

NCT00854789 | Completed Phase 1

• 1 other identifier: 03-20012
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 2

Brief Summary

The objectives of this study are the following:

1. 1.To assess safety and document local and systemic toxicity to the peptide vaccine (E75) in node-negative breast cancer patients.
2. 2.To determine the optimal dose of the immunoadjuvant, GM-CSF, necessary to elicit an in vivo cellular immune response to the peptide vaccine yet limit toxicity.
3. 3.To determine the optimal inoculation schedule to elicit an in vivo cellular immune response to the peptide vaccine.
4. 4.To correlate the efficiency of eliciting an in vivo cellular immune response to the peptide vaccine with the degree of HER2/neu expression in the patient's tumor.

Conditions

Breast Cancer

Keywords

Breast cancer

Outcome Measures

Primary Outcomes (1)

• The primary endpoints are the safety and optimal dosing of the vaccine to induce an in vivo peptide-specific immune response.

  Time period needed to determine the maximum tolerated and optimal biologic doses (30 days after each monthly dose)

Secondary Outcomes (1)

• Time to recurrence is measured as a secondary outcome measure.

  30 days after each monthly vaccine, then per standard of care for breast cancer.

Study Arms (2)

Vaccine

EXPERIMENTAL

HLA-A2+ and HLA-A3+ patients are administered the E75+GM-CSF vaccine.

Biological: E75 + GM-CSF vaccine

Control/observation

NO INTERVENTION

HLA-A2- and HLA-A3- patients are prospectively followed for disease recurrence. Control patients are not vaccinated.

Interventions

E75 + GM-CSF vaccine BIOLOGICAL

The 1 ml by volume vaccine is administered intradermally in 0.5 ml inoculums at two different sites within 5 cm of each other on an extremity. Vaccinations will be given according to the schedule the patient has been assigned and will be administered in the same lymph node draining area (same arm or thigh). In addition, an optional booster inoculation as requested by previously vaccinated patients will be offered every 6 months for the duration of the protocol. The dose will be determined by the PI based on the patient's response to the initial vaccination series.

Vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Breast cancer and negative lymph nodes
• HLA-A2+ and/or HLA-A3+ to receive the vaccine. HLA-A2-, HLA-A3- patients will be eligible to be included in the control group.
• Immunologically intact with a good performance status (defined below).
• Without evidence of disease.
• Patients may enroll while receiving appropriate hormonal therapy for their disease.
• Completion of all standard first-line therapies (but may still be on hormonal therapy)

You may not qualify if:

• HLA-A2- and/or HLA-A3- patients will not be vaccinated
• Anergic by the Mantoux panel of recall antigens
• Receiving immunosuppressive therapy
• In poor health (Karnofsky \<60%, ECOG \>2)
• Tbili \>1.5 mg/dL and creatinine\>2 mg/dL
• Pregnancy (urine HCG)
• Active metastatic disease
• Involved in other experimental protocols (unless approval is first obtained by the other study PI)
• Refusal of standard therapies

Sponsors & Collaborators

• COL George Peoples, MD, FACS: lead
• Uniformed Services University of the Health Sciences: collaborator

Study Sites (2)

Walter Reed Army Medical Center

Washington D.C., District of Columbia, 20307-5001, United States

Location

Windber Medical Center

Windber, Pennsylvania, 15963, United States

Location

Related Publications (18)

• Mittendorf EA, Storrer CE, Shriver CD, Ponniah S, Peoples GE. Investigating the combination of trastuzumab and HER2/neu peptide vaccines for the treatment of breast cancer. Ann Surg Oncol. 2006 Aug;13(8):1085-98. doi: 10.1245/ASO.2006.03.069. Epub 2006 Jul 24.

  PMID: 16865596 BACKGROUND

• Dehqanzada ZA, Storrer CE, Hueman MT, Foley RJ, Harris KA, Jama YH, Kao TC, Shriver CD, Ponniah S, Peoples GE. Correlations between serum monocyte chemotactic protein-1 levels, clinical prognostic factors, and HER-2/neu vaccine-related immunity in breast cancer patients. Clin Cancer Res. 2006 Jan 15;12(2):478-86. doi: 10.1158/1078-0432.CCR-05-1425.

  PMID: 16428490 BACKGROUND

• Woll MM, Fisher CM, Ryan GB, Gurney JM, Storrer CE, Ioannides CG, Shriver CD, Moul JW, McLeod DG, Ponniah S, Peoples GE. Direct measurement of peptide-specific CD8+ T cells using HLA-A2:Ig dimer for monitoring the in vivo immune response to a HER2/neu vaccine in breast and prostate cancer patients. J Clin Immunol. 2004 Jul;24(4):449-61. doi: 10.1023/B:JOCI.0000029117.10791.98.

  PMID: 15163902 BACKGROUND

• Peoples GE, Gurney JM, Hueman MT, Woll MM, Ryan GB, Storrer CE, Fisher C, Shriver CD, Ioannides CG, Ponniah S. Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients. J Clin Oncol. 2005 Oct 20;23(30):7536-45. doi: 10.1200/JCO.2005.03.047. Epub 2005 Sep 12.

  PMID: 16157940 RESULT

• Mittendorf EA, Gurney JM, Storrer CE, Shriver CD, Ponniah S, Peoples GE. Vaccination with a HER2/neu peptide induces intra- and inter-antigenic epitope spreading in patients with early stage breast cancer. Surgery. 2006 Mar;139(3):407-18. doi: 10.1016/j.surg.2005.06.059.

  PMID: 16546506 RESULT

• Hueman MT, Stojadinovic A, Storrer CE, Dehqanzada ZA, Gurney JM, Shriver CD, Ponniah S, Peoples GE. Analysis of naive and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine. Cancer Immunol Immunother. 2007 Feb;56(2):135-46. doi: 10.1007/s00262-006-0188-9. Epub 2006 Jun 17.

  PMID: 16783576 RESULT

• Dehqanzada ZA, Storrer CE, Hueman MT, Foley RJ, Harris KA, Jama YH, Shriver CD, Ponniah S, Peoples GE. Assessing serum cytokine profiles in breast cancer patients receiving a HER2/neu vaccine using Luminex technology. Oncol Rep. 2007 Mar;17(3):687-94.

  PMID: 17273752 RESULT

• Stojadinovic A, Mittendorf EA, Holmes JP, Amin A, Hueman MT, Ponniah S, Peoples GE. Quantification and phenotypic characterization of circulating tumor cells for monitoring response to a preventive HER2/neu vaccine-based immunotherapy for breast cancer: a pilot study. Ann Surg Oncol. 2007 Dec;14(12):3359-68. doi: 10.1245/s10434-007-9538-x. Epub 2007 Sep 29.

  PMID: 17906897 RESULT

• Peoples GE, Holmes JP, Hueman MT, Mittendorf EA, Amin A, Khoo S, Dehqanzada ZA, Gurney JM, Woll MM, Ryan GB, Storrer CE, Craig D, Ioannides CG, Ponniah S. Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clin Cancer Res. 2008 Feb 1;14(3):797-803. doi: 10.1158/1078-0432.CCR-07-1448.

  PMID: 18245541 RESULT

• Amin A, Benavides LC, Holmes JP, Gates JD, Carmichael MG, Hueman MT, Mittendorf EA, Storrer CE, Jama YH, Craig D, Stojadinovic A, Ponniah S, Peoples GE. Assessment of immunologic response and recurrence patterns among patients with clinical recurrence after vaccination with a preventive HER2/neu peptide vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer Immunol Immunother. 2008 Dec;57(12):1817-25. doi: 10.1007/s00262-008-0509-2. Epub 2008 Apr 8.

  PMID: 18392824 RESULT

• Mittendorf EA, Holmes JP, Ponniah S, Peoples GE. The E75 HER2/neu peptide vaccine. Cancer Immunol Immunother. 2008 Oct;57(10):1511-21. doi: 10.1007/s00262-008-0540-3. Epub 2008 Jun 7.

  PMID: 18536917 RESULT

• Holmes JP, Gates JD, Benavides LC, Hueman MT, Carmichael MG, Patil R, Craig D, Mittendorf EA, Stojadinovic A, Ponniah S, Peoples GE. Optimal dose and schedule of an HER-2/neu (E75) peptide vaccine to prevent breast cancer recurrence: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer. 2008 Oct 1;113(7):1666-75. doi: 10.1002/cncr.23772.

  PMID: 18726994 RESULT

• Holmes JP, Clifton GT, Patil R, Benavides LC, Gates JD, Stojadinovic A, Mittendorf EA, Ponniah S, Peoples GE. Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer. 2011 Feb 1;117(3):463-71. doi: 10.1002/cncr.25586. Epub 2010 Sep 15.

  PMID: 20845479 RESULT

• Patil R, Clifton GT, Holmes JP, Amin A, Carmichael MG, Gates JD, Benavides LH, Hueman MT, Ponniah S, Peoples GE. Clinical and immunologic responses of HLA-A3+ breast cancer patients vaccinated with the HER2/neu-derived peptide vaccine, E75, in a phase I/II clinical trial. J Am Coll Surg. 2010 Feb;210(2):140-7. doi: 10.1016/j.jamcollsurg.2009.10.022. Epub 2009 Dec 22.

  PMID: 20113933 RESULT

• Mittendorf EA, Clifton GT, Holmes JP, Clive KS, Patil R, Benavides LC, Gates JD, Sears AK, Stojadinovic A, Ponniah S, Peoples GE. Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer. 2012 May 15;118(10):2594-602. doi: 10.1002/cncr.26574. Epub 2011 Oct 11.

  PMID: 21989902 RESULT

• Benavides LC, Sears AK, Gates JD, Clifton GT, Clive KS, Carmichael MG, Holmes JP, Mittendorf EA, Ponniah S, Peoples GE. Comparison of different HER2/neu vaccines in adjuvant breast cancer trials: implications for dosing of peptide vaccines. Expert Rev Vaccines. 2011 Feb;10(2):201-10. doi: 10.1586/erv.10.167.

  PMID: 21332269 RESULT

• Benavides LC, Gates JD, Carmichael MG, Patil R, Holmes JP, Hueman MT, Mittendorf EA, Craig D, Stojadinovic A, Ponniah S, Peoples GE. The impact of HER2/neu expression level on response to the E75 vaccine: from U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clin Cancer Res. 2009 Apr 15;15(8):2895-904. doi: 10.1158/1078-0432.CCR-08-1126. Epub 2009 Apr 7.

  PMID: 19351776 RESULT

• Hueman MT, Stojadinovic A, Storrer CE, Foley RJ, Gurney JM, Shriver CD, Ponniah S, Peoples GE. Levels of circulating regulatory CD4+CD25+ T cells are decreased in breast cancer patients after vaccination with a HER2/neu peptide (E75) and GM-CSF vaccine. Breast Cancer Res Treat. 2006 Jul;98(1):17-29. doi: 10.1007/s10549-005-9108-5. Epub 2006 Jun 7.

  PMID: 16758122 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• George E Peoples, MD

  Cancer Vaccine Development Program

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Surgical Oncology, Brooke Army Medical Center; Director and Principal Investigator, Cancer Vaccine Development Program

Study Record Dates

• First Submitted: March 2, 2009
• First Posted: March 3, 2009
• Study Start: December 1, 2002
• Primary Completion: May 1, 2012
• Study Completion: March 1, 2013
• Last Updated: March 31, 2020

Record last verified: 2020-03

Locations

US (2)