Vaccination of Patients With Breast Cancer With Dendritic Cell/Tumor Fusions and IL-12

Study Overview
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Brief Summary
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The purpose of this study is to test the safety of an investigational Dendritic Cell/Tumor Fusion vaccine given with IL-12 for patients with breast cancer. RATIONALE: Vaccines made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells. Interleukin-12 may stimulate the white blood cells to kill tumor cells. Giving vaccine therapy together with interleukin-12 may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of interleukin-12 when given together with vaccine therapy and to see how well they work in treating women with stage IV breast cancer.

Detailed Description
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TUMOR COLLECTION: Tumor cells will be collected from the participant to make the study vaccine. Based on the location of the tumor, a decision will be made as to the best approach to obtain these cells. DENDRITIC CELL COLLECTION: Participants will undergo a procedure known as leukapheresis to obtain their dendritic cells (this procedure may be done before or after the tumor cells have been obtained). This procedure takes about 2-4 hours. If not enough cells are collected, the participant may be asked to return for an additional leukapheresis procedure. If sufficient number of cells are obtained, tumor cells and dendritic cells will then be fused (combined together to make one larger cell) together in the laboratory and divided into the appropriate dose for administration. TREATMENT: Treatment will consist of an injection of tumor cells fused with dendritic cells under the skin every 3 weeks for a total of 9 weeks. The dose that the participant receives will depend on the total number of fusion cells that are made. STUDY COHORTS: The first group of three participants will receive the DC/Tumor Fusion study vaccine alone. The next group of 3 participants will receive the DC/Tumor Fusion study vaccine with a low dose of Il-12. If there are no significant side effects the following groups of subjects will be treated with the DC/Tumor Fusion study vaccine and a higher dose of Il-12. PATIENT MONITORING: Participants will be carefully monitored during the study period and the following tests and procedures will be performed: physical exams (weekly); blood collections (weekly); DC/Tumor Fusion study vaccine Journal (for the participant to record any side effects or other medications they may be taking); tumor cells skin test (before the first vaccine and one month following the last vaccine); skin biopsy at the site of the vaccination administration, accessible tumor site, or if there is a local reaction site.

Official Title
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Vaccination of Patients With Breast Cancer With Dendritic Cell/Tumor Fusions and IL-12

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: Dendritic Cell/Tumor Fusion Vaccine
* Drug: Interleukin-12
* Drug: Interleukin-12


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage IV breast cancer with measurable disease and accessible tumor ECOG Performance Status 0-2 with greater than six week life expectancy 18 years of age or older Laboratory values as outlined in the protocol Exclusion Criteria: Patients must not have received other immunotherapy treatment in the three months prior to the initial vaccination Patients may not be on herceptin therapy during this protocol and may not have received it for four weeks prior to initial vaccination Patients must not have received weekly chemotherapy or hormonal treatment for two weeks prior to the initial vaccination and must not have received monthly chemotherapy for four weeks prior to the initial vaccination Clinical evidence of CNS disease Clinically significant autoimmune disease Patients who are HIV+ Serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failure Pregnant of lactating women will be excluded, all premenopausal women must undergo pregnancy testing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Dendritic Cell/Tumor Fusion Vaccine Only | Biological: Dendritic Cell/Tumor Fusion Vaccine<br>* Vaccine is derived from the participants dendritic cells and tumor cells<br>* Other names: DC/tumor cell fusion vaccine;|
| Experimental: Group 2<br>Dendritic Cell/tumor fusion vaccine and low dose IL-12 | Biological: Dendritic Cell/Tumor Fusion Vaccine<br>* Vaccine is derived from the participants dendritic cells and tumor cells<br>* Other names: DC/tumor cell fusion vaccine;Drug: Interleukin-12<br>* Given subcutaneously at dose of 30ng/kg<br>* Other names: rhIL-12;|
| Experimental: Group 3<br>Dendritic Cell/tumor fusion vaccine and higher dose IL-12 | Biological: Dendritic Cell/Tumor Fusion Vaccine<br>* Vaccine is derived from the participants dendritic cells and tumor cells<br>* Other names: DC/tumor cell fusion vaccine;Drug: Interleukin-12<br>* Given subcutaneously at dose of 100ng/kg<br>* Other names: rhIL-12;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events Associated With Vaccination of Breast Cancer Patients With Dendritic Cell (DC)/Tumor Fusion Vaccine | Using CTCAE version 3, adverse events associated with the intervention were captured throughout the treatment portion of the study. All adverse events were then compiled and the number of patients who experienced these adverse events was recorded. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Determine if Cellular and Humoral Immunity is Induced by Serial Vaccination With DC/Tumor Fusion Cells and rhIL-12. | This outcome was not measured because no patients were treated with rhIL-12. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer, dendritic cell vaccine, tumor fusion vaccine, IL-12