Breast Cancer
Conditions
Keywords
Breast cancer
Brief 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
Detailed 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.
Interventions
BIOLOGICALE75 + 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.
Sponsors
Uniformed Services University of the Health Sciences
COL George Peoples, MD, FACS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| The clinical endpoint is time to disease recurrence. | 30 days after each monthly vaccine, then per standard of care for breast cancer. |
Countries
United States
Outcome results
None listed