Safety and Efficacy Study of HER2/Neu (E75) Vaccine in Node-Positive Breast Cancer Patients

Breast Cancer Clinical Trial

Official title:

Phase Ib Trial of HER2/Neu Peptide (E75) Vaccine in Breast Cancer Patients at Risk for Recurrence After Surgical and Medical Therapies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00841399
• Other study ID #: 00-2005
• Secondary ID: WRAMC 20280
• Status: Completed
• Phase: Phase 1
• Start date: July 2001
• Est. completion date: March 2013

Study information

• Verified date: March 2020
• Source: Walter Reed Army Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purposes of this study are the following:

1. To assess safety and document local and systemic toxicity to the peptide vaccine (E75)

2. To determine maximum tolerated dose (MTD) and optimal biologic dose (OBD) for the peptide vaccine

3. To evaluate the in vivo cellular immune response to the peptide vaccine

4. To evaluate time to recurrence in the vaccinated patients vs. matched controls

Description:

Breast cancer is the most common malignancy and second most common cause of cancer-specific death among women in the United States. Despite advances in the diagnosis and treatment of breast cancer, one third of the women who develop the disease will die of the disease, accounting for approximately 46,300 deaths/year. While good primary therapies are available to treat early stage breast cancer, there is a substantial failure rate to these therapies in more advanced disease.

Advances in the understanding of the immune response to cancer have lead to the genesis of immunotherapeutic approaches. Specifically, the development of anti-cancer vaccines holds promise as an adjuvant and preventive therapy for patients after both primary surgical and medical treatment for breast cancer, but who are at a high risk for recurrence. Patients with greater than four lymph nodes positive have an 87% chance of recurrence post standard surgical and medical therapies at 10 years. While patients with hormone receptor positive tumors have the option to undergo hormonal therapy, recurrence is especially high among estrogen receptor/progesterone receptor (ER/PR) negative patients. For these patients, currently there is no good treatment option after completion of primary therapy; close surveillance and watchful waiting is the standard.

It is this population of patients that a vaccine strategy to induce cellular immunity would target. We propose to vaccinate these patients with an immunogenic peptide from the HER2/neu protein. If successful, this vaccine strategy could be utilized as an adjuvant to currently accepted first line therapy in future clinical trials.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: March 2013
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. HER2/neu expressing tumor

2. 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.

3. Immunologically intact with a good performance status

4. Identified as being high or intermediate risk for recurrence

5. Without evidence of disease

6. Completion of all standard first-line therapies (but may still be on hormonal therapy)

Exclusion Criteria:

1. Tumor does not express HER2/neu

2. Not HLA-A2+ and/or HLA-A3+

3. Anergic

4. Receiving immunosuppressive therapy

5. In poor health (Karnofsky <60%, ECOG >2 and Tbili >1.5 and creatinine>2)

6. Pregnant (beta HCG+)

7. Metastatic disease or have refused standard therapies

8. Patients enrolled in other experimental protocols may enroll to this study only with the permission of the other study PI.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• E75 + GM-CSF vaccine
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.

Locations

Country	Name	City	State
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Windber Medical Center	Windber	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
COL George Peoples, MD, FACS	Uniformed Services University of the Health Sciences

Country where clinical trial is conducted

United States, 

References & Publications (18)

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 aft — View Citation

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 Trial — View Citation

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 Vac — View Citation

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. — View Citation

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. — View Citation

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 Trial — View Citation

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 Canc — View Citation

Hueman MT, Stojadinovic A, Storrer CE, Dehqanzada ZA, Gurney JM, Shriver CD, Ponniah S, Peoples GE. Analysis of naïve and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine. Cancer Immunol — View Citation

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. B — View Citation

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 Mili — View Citation

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. — View Citation

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. Review. — View Citation

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. Epub 2006 Jul 24. — View Citation

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/I — View Citation

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):7 — View Citation

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 — View Citation

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 — View Citation

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. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The clinical endpoint is time to disease recurrence.		30 days after each monthly vaccine, then per standard of care for breast cancer.