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

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

The purposes of this study are the following: To assess safety and document local and systemic toxicity to the peptide vaccine (E75) To determine maximum tolerated dose (MTD) and optimal biologic dose (OBD) for the peptide vaccine To evaluate the in vivo cellular immune response to the peptide vaccine To evaluate time to recurrence in the vaccinated patients vs. matched controls

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.

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.

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

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.

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

Inclusion Criteria: 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) Exclusion Criteria: 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.

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