HER-2 Pulsed DC Vaccine to Prevent Recurrence of Invasive Breast Cancer Post Neoadjuvant Chemotherapy

Study Overview
=================
Brief Summary
-----------------
The primary goals of this trial will be to determine the safety and immune activity of HER-2 pulsed DC1 vaccine in patients with high risk HER-2pos breast cancer with residual disease post neoadjuvant therapy. Investigators will also explore the possibility of determining whether circulating tumor cells can be used as surrogate to assess response to vaccination.

Detailed Description
-----------------
Dendritic cell cancer vaccines combined with chemotherapy may increase complete responses giving breast cancer specific immune cells greater opportunity to function while the immune repertoire is being shifted by chemotherapy to anti-breast cancer response and offer the chance to test secondary prevention of breast cancer in high risk settings. There is a need to determine whether this ICAIT DC1 can activate CD4 and CD8 T cells prior to or in combination with chemotherapy with or without added trastuzumab. This study began at the Abramson Cancer Center of the University of Pennsylvania and will be continued at H. Lee Moffitt Cancer Center and Research Institute.

Official Title
-----------------
Pilot Phase I HER-2 Pulsed DC Vaccine to Prevent Recurrence for Patients With HER-2 Driven High Risk Invasive Breast Cancer Post Neoadjuvant Chemotherapy

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Biological: HER-2 pulsed Dendritic Cell Vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women ≥ 18 years. HER-2 expressing stage I - III breast cancer with residual disease in the breast or axillary nodes post-neoadjuvant chemotherapy. Women of childbearing age with a negative pregnancy serum test documented prior to enrollment. Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0 or 1. Women of childbearing potential must agree to use a medically acceptable form of birth control during their participation in the study. Have voluntarily signed a written Informed Consent in accordance with institutional policies after its contents have been fully explained to them. Exclusion Criteria: Pregnant or lactating. Positive for HIV or hepatitis C at baseline by self report. Potential participants with coagulopathies, including thrombocytopenia with platelet count <75,000, INR > 1.5 and partial thromboplastin time > 50 sec. Potential participants with MUGA < 50% EF. Pre-existing medical illnesses or medications which might interfere with the study as determined by Principal Investigator (PI).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HER-2 Pulsed Dendritic Cell Vaccine<br>6 weekly HER-2 pulsed dendritic cell vaccines followed by 3 booster vaccines once every 3 months. | Biological: HER-2 pulsed Dendritic Cell Vaccine<br>* Each dose will consist of between 1.0-2.0 x 10^7 cells and will be injected into 1-2 different normal groin lymph nodes or axillary nodes.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participation Compliance | Feasibility: Defined as a patient's ability and willingness to complete the treatment regimen (6 weekly vaccinations). Data collection will include rate of successful completion and occurrence rate for each reason stated for non-completion. | Up to 18 months | 
| Occurrence of Treatment Related Adverse Events | Number of participants with treatment related adverse events, per event category. | Up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | Immunogenicity will be evaluated by descriptive statistics, plots of pre- and post-treatment values and fold changes. Immune response rate and 95% exact confidence interval will be calculated. | Up to 5 years follow-up | 
| Anti-HER2 Immunity | Anti-HER2 response will be quantitated as EOS/baseline fold change in dilution studies. | Up to 5 years follow-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Invasive Breast Cancer, Breast Cancer, Immunotherapy, Vaccine, Dendritic Cell, Neoadjuvant