Pilot Study of a Breast Cancer Vaccine Plus Poly-ICLC for Breast Cancer

Study Overview
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Brief Summary
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Despite advances in surgical, radiation and medical therapies of early stage breast cancer, some patients will experience disease recurrence. Because recurrence may not happen for years after definitive treatment, there is a period of time between resection and relapse when micrometastatic disease may be amenable to immune eradication or modulation. While the ultimate goal of any cancer treatment is clinical efficacy, the immediate urgency in breast immunotherapy is to define treatments that have immunologic efficacy. In this study, the investigators will determine whether a vaccine consisting of nine-class I breast specific peptides plus a class II tetanus toxoid helper peptide is immunogenic when administered with poly-ICLC to participants with stage IB to IIIA breast cancer in the adjuvant setting.

Detailed Description
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The study is a single arm, open label, pilot study of safety and immune efficacy of peptide vaccination with poly-ICLC in patients with stage IB-IIIA resected breast cancer. Participants will be patients who have completed their last dose/treatment of any single treatment or combination of adjuvant surgery, radiation, chemotherapy or trastuzumab therapy between 45 days and 6 months (180 days) prior to enrollment. Each vaccination will be administered on days 1, 8, 15, 36, 57, and 78. All participants will receive 9 class I MHC-restricted synthetic peptides (restricted by HLA-A1, -A2, -A3, or -A31) and a class II MHC-restricted tetanus helper peptide mixed with 1mg poly-ICLC and administered in sterile water. The vaccine will be administered intramuscular (IM) (1 ml) and intradermally (ID) (1 ml) at vaccination sites in the arm and leg. (Each vaccine given IM and ID at one site; site to alternate between arm site opposite the breast cancer and an anterior thigh site.) Participants will be screened for HLA type and must be HLA-A1, -A2, -A3, or -A31 (80% of the Virginia population in prior studies1). Annual follow-up for progression and survival for 3 years after study withdrawal/completion.

Official Title
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A Pilot Study of the Immunogenicity of a 9-Peptide Breast Cancer Vaccine Plus Poly-ICLC in Stage I-IV Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: poly-ICLC
* Biological: 9 Peptides from Her-2/neu, CEA, & CTA
* Biological: Peptide-tet


Participation Criteria
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Eligibility Criteria
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Inclusion: Patients who have been diagnosed with clinical or pathologic stage I to stage IV adenocarcinoma of the breast (any subtype) who have undergone, and recovered from primary therapy (any combination of surgery, radiation, and/or chemotherapy and/or HER2-directed therapy), with their last dose/treatment (of any single or combination treatment) being between 28 days and 36 months prior to enrollment. Staging will be based on the Seventh Edition AJCC staging system. (Systemic staging with CT or PET scans is not required by AJCC and is not required or exclusionary for this trial). Stage IA patients must be high risk based upon triple negative status or HER2+ status Patients may or may not be receiving hormonal therapy at the time of study entry. Age ≥ 18 years at the time of enrollment ECOG performance status of 0 or 1 Ability and willingness to give informed consent HLA-A1, -A2, -A3, or -A31 positive Adequate organ function HIV and Hepatitis C negative Subjects must have a minimum of two intact lymph node basins (any combination of axillary and inguinal basins that have not undergone complete nodal dissection) Exclusion Criteria Known or suspected allergies to any component of the vaccine Active infection requiring antibiotics are excluded. The following medications or treatments within the 4 weeks (28 days) prior to consenting. These medication and treatments may not be re-started at any time throughout the study in order to remain eligible. Breast tumor resection surgery (reconstructive surgery permitted) Chemotherapy Radiation therapy Allergy desensitization injections Growth factors (e.g., Procrit®, Aranesp®, Neulasta®) Other agents with putative immunomodulating activity (with the exception of non-steroidal anti-inflammatory agents) Any investigational medication Tthe following medications or treatments within the 4 weeks (28 days) prior to consenting: Corticosteroids, administered parenterally, orally, or inhaled (Inhaled steroids, such as: Advair®, Flovent®, Azmacort.®) Topical corticosteroids are acceptable. Previous vaccination with any of the synthetic peptides included in this protocol. Active tuberculosis and not on active antitubercular agents Pregnancy. Female subjects must not be breastfeeding A medical contraindication or potential problem in complying with the requirements of the protocol, in the opinion of the investigator New York Heart Association classification as having Class III or IV heart disease Stage IV subjects who have anticipated chemotherapy need within the 108 day treatment period for this trial. Subjects that have experienced active autoimmune disorders requiring cytotoxic or immunosuppressive therapy within the 6 weeks (42 days) prior to consenting. The following will not be exclusionary: The presence of laboratory evidence of autoimmune disease (e.g., positive ANA titer) without symptoms Clinical evidence of vitiligo Other forms of depigmenting illness Mild arthritis requiring NSAID medications

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 9 Peptides from Her-2/neu, CEA, & CTA, peptide-tet, poly-ICLC<br>9 class I MHC-restricted synthetic peptides (100 mcg each peptide) derived from breast cancer associated proteins, a class II MHC-restricted tetanus derived peptide (200 mcg), plus polyICLC (1 mg). | Biological: poly-ICLC<br>* poly-ICLC<br>Biological: 9 Peptides from Her-2/neu, CEA, & CTA<br>* 9 synthetic peptides derived from Her-2/neu, CEA & CTA derived breast cancer proteins.<br>Biological: Peptide-tet<br>* A class II MHC-restricted helper peptide derived from tetanus toxoid protein.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (Frequency of dose limiting adverse events) |  | 30 days post-administration of the last vaccine | 
| Immune response rate | Measured as the number of IFN-gamma producing cells in the blood in response to the vaccine. | through day 108 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (adverse event profile) |  | 30 days post-administration of the last vaccine | 
| Immunogenicity- CD8+ T cell specificity | Characterize vaccine specific peripheral CD8+ T-cell specificity by tetramer staining and flow cytometric analysis | through day 108 | 
| Immunogenicity- CD8+ cytokine production | Estimate the Tc1/Tc2 cytokine production bias of circulating vaccine-specific T cells. | through day 108 | 
| Immunogenicity- immue responses among subjects treated with anti-estrogen therapies | Using the ELIspot assay, describe the frequency of immune responses among patients treated with anti-estrogen therapies | through day 108 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, peptide vaccine, immunotherapy