Trial With Autologous Dendritic Cell Vaccination in Patients With Stage II-III HER2 Negative Breast Cancer

Study Overview
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Brief Summary
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Molecular expression in breast cancer (BC) defines special fenotypes with different prognostic and predictive features.Since the addition of trastuzumab and lapatinib to chemotherapy, HER2 overexpressing tumors have become the best responders to systemic therapies, reaching pathologic complete response rates (pCR) around 50%. But HER2 negative tumors (luminal A and triple negative) are characterized by low chemosensitivity (luminal A) or early distant relapse after diagnosis (triple negative BC) . In this open, prospective, non-randomized and multicentric phase II study the investigators include stage II and III HER2 negative BC patients that are going to receive neoadjuvant sequential chemotherapy Epirubicin+Ciclofosfamide x 4 and then Docetaxel x 4)with an individualized vaccination with autologous dendritic cells pulsed with their own tumor. The hypothesis is that the reinforcement of the immune system with the autologous dendritic cell vaccination against HER2 negative BC could increase pathologic complete responses (pCR) and disease free survival(DFS), when added to chemo, surgery and radiation therapy and in a maintenance schedule.

Detailed Description
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Chemotherapy schedule: dose dense epirubucin 100 mgr/m2 plus ciclofosfamide 600 mgr/m2 every two weeks for four cycles with with GM-CSF support on day +1 (pegylated filgastrim) or on days +5 to +9 (filgastrim) subcutaneously docetaxel 80-100 mgr/m2 every three weeks for four cycles. Addition of GM-CSF if docetaxel doses are > 85 mgr/m2

Official Title
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Phase II Trial With Autologous Dendritic Cell Vaccination in Patients With Stage II-III HER2 Negative Breast Cancer

Conditions
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Stage II Breast Cancer, Stage III Breast Cancer

Intervention / Treatment
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* Biological: Autologous dendritic cell vaccination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HER2 negative and stage II and III Breast cancer patients who benefit with neoadjuvant chemotherapy age 18-75 to get enough tumoral sample to elaborate the vaccine Exclusion Criteria: pregnancy severe diseases hepatitis or HIV need to be on immunosuppressant drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: DENDRITIC CELL VACCINATION<br>Px will receive standard neoadjuvant chemotherapy plus active vaccination. we will compare results with an historic cohort of patients treated with the same chemotherapy without the vaccines | Biological: Autologous dendritic cell vaccination<br>* Autologous dendritic cell vaccination. Dendritic cells are pulsed with their own tumor antigens<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathologic complete response (pCR) in the breast and the axilla |  | 6 months after starting chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | During the 6-24 months of administration of the vaccine | 
| Impact of the vaccine on patients DFS and OS | We will compare our cohort of patients vaccinated and treated with chemotherapy, surgery and radiation therapy with an historic cohort in our center treated with the same schedule of chemotherapy , surgery and radiation therapy without the vaccine | three to five years after the diagnosis of breast cancer | 
| EORTC quality of life |  | From 9 months and up to two years | 
| Correlation among the specific immune response induced in patients and the pathologic response of the tumor | Specific immune response will be evaluated as delayed hipesrsensitivity (DTH), humoral response by cuantification antibodies against tumoral cells (ELISA)and cellullar response (proliferation assay and citokines production) | 6-24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, neoadjuvant chemotherapy, autologous dendritic cell vaccination