NCT00841399

Brief Summary

The purposes of this study are the following:

  1. 1.To assess safety and document local and systemic toxicity to the peptide vaccine (E75)
  2. 2.To determine maximum tolerated dose (MTD) and optimal biologic dose (OBD) for the peptide vaccine
  3. 3.To evaluate the in vivo cellular immune response to the peptide vaccine
  4. 4.To evaluate time to recurrence in the vaccinated patients vs. matched controls

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P75+ for phase_1 breast-cancer

Timeline
Completed

Started Jul 2001

Longer than P75 for phase_1 breast-cancer

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2001

Completed
7.6 years until next milestone

First Submitted

Initial submission to the registry

February 10, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 11, 2009

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2012

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2013

Completed
Last Updated

March 31, 2020

Status Verified

March 1, 2020

Enrollment Period

11.2 years

First QC Date

February 10, 2009

Last Update Submit

March 28, 2020

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.

Secondary Outcomes (1)

  • The clinical endpoint is time to disease recurrence.

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

Study Arms (2)

E75 + GM-CSF vaccine

EXPERIMENTAL

The dose escalation scheme is for three patients to receive each of the doses, 100, 500, and 1,000 mcg of peptide + 250 mcg GM-CSF each month for 6 months until the maximum tolerated dose is determined. Patients who receive the vaccine are HLA-A2+ and/or HLA-A3+. Responses to the vaccine are measured via immunologic assays.

Biological: E75 + GM-CSF vaccine

Control/observation

NO INTERVENTION

HLA-A2- and HLA-A3- patients do not receive the E37 + GM-CSF vaccine, but are instead enrolled to the control arm for observation.

Interventions

E75 + GM-CSF vaccineBIOLOGICAL

Dose escalation scheme involving three patients each receiving injection of 100, 500, or 1,000 mcg E75 + GM-CSF monthly for 6 months. HLA-A2 and HLA-A3 status determined. HLA-A2+ and HLA-A3+ patients receive the vaccine; HLA-A2- and HLA-A3- enrolled to the control arm.

E75 + GM-CSF vaccine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • HER2/neu expressing tumor
  • HLA-A2+ and/or HLA-A3+ to receive the vaccine. HLA-A2- and/or HLA-A3- patients will be eligible to be included in the control group.
  • Immunologically intact with a good performance status
  • Identified as being high or intermediate risk for recurrence
  • Without evidence of disease
  • Completion of all standard first-line therapies (but may still be on hormonal therapy)

You may not qualify if:

  • Tumor does not express HER2/neu
  • Not HLA-A2+ and/or HLA-A3+
  • Anergic
  • Receiving immunosuppressive therapy
  • In poor health (Karnofsky \<60%, ECOG \>2 and Tbili \>1.5 and creatinine\>2)
  • Pregnant (beta HCG+)
  • Metastatic disease or have refused standard therapies
  • Patients enrolled in other experimental protocols may enroll to this study only with the permission of the other study PI.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

Windber Medical Center

Windber, Pennsylvania, 15963, United States

Location

Related Publications (19)

  • 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: 16865596BACKGROUND

  • 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: 16428490BACKGROUND

  • 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: 15163902BACKGROUND

  • 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: 16157940RESULT

  • 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: 16546506RESULT

  • 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: 16783576RESULT

  • 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: 17273752RESULT

  • 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: 17906897RESULT

  • 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: 18245541RESULT

  • 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: 18392824RESULT

  • 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: 18536917RESULT

  • 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: 18726994RESULT

  • 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: 20845479RESULT

  • 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: 20113933RESULT

  • 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: 21989902RESULT

  • 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: 21332269RESULT

  • 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: 19351776RESULT

  • 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: 16758122RESULT

  • Mittendorf EA, Clifton GT, Holmes JP, Schneble E, van Echo D, Ponniah S, Peoples GE. Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. Ann Oncol. 2014 Sep;25(9):1735-1742. doi: 10.1093/annonc/mdu211. Epub 2014 Jun 6.

    PMID: 24907636DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin 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

Study Record Dates

First Submitted

February 10, 2009

First Posted

February 11, 2009

Study Start

July 1, 2001

Primary Completion

September 1, 2012

Study Completion

March 1, 2013

Last Updated

March 31, 2020

Record last verified: 2020-03

Locations

US(2)