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

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

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.

Study Overview

• Status: Completed
• Conditions: Stage II Breast Cancer; Stage III Breast Cancer
• Intervention / Treatment: Biological: Autologous dendritic cell vaccination

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DENDRITIC CELL VACCINATION; 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; Autologous dendritic cell vaccination. Dendritic cells are pulsed with their own tumor antigens

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Collaborators: National Institutes of Health (NIH); Spanish Clinical Research Network - SCReN
• Investigators: Principal Investigator: Marta Santisteban, MD, PhD., Clinica Universidad de Navarra

Publications and helpful links

General Publications

• Santisteban M, Solans BP, Hato L, Urrizola A, Mejias LD, Salgado E, Sanchez-Bayona R, Toledo E, Rodriguez-Spiteri N, Olartecoechea B, Idoate MA, Lopez-Diaz de Cerio A, Inoges S. Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis. Ther Adv Med Oncol. 2021 Dec 23;13:17588359211064653. doi: 10.1177/17588359211064653. eCollection 2021.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: April 1, 2011
• First Submitted That Met QC Criteria: September 8, 2011
• First Posted (Estimate): September 9, 2011

Study Record Updates

• Last Update Posted (Estimate): May 19, 2016
• Last Update Submitted That Met QC Criteria: May 18, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: breast cancer; neoadjuvant chemotherapy; autologous dendritic cell vaccination
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: DEND/CM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: By 2017 scientific data should be communicated