Breast Cancer Neoantigen Vaccination With Autologous Dendritic Cells

June 15, 2022 updated by: Universidad Nacional de Colombia

Phase I Clinical Study of Immunotherapy With Personalized Synthetic Vaccines in Patients With Triple Negative Breast Cancer

In this project, the investigators propose the first clinical study in Colombia of vaccination of patients with triple-negative breast cancer (TNBC) using synthetic peptides that contain mutations of the tumor itself that will be presented to the immune system by autologous dendritic cells to assess immunogenicity and safety of this type of personalized vaccine. Achieving the specific objectives set out in this project will mean that the investigators can validate in Colombia the experimental design necessary to identify exclusive epitopes in the tumors of the participants in this study, and also that have been able to demonstrate the safety and immunogenicity of these vaccines.

Study Overview

Detailed Description

EXECUTIVE SUMMARY.

The achievements of personalized medicine in cancer research in developed countries make envision that various types of cancer in an advanced stage, will be in the medium term treatable diseases. The discovery of new therapies is the product of the achieved development of Translational Medicine (the laboratory findings translated in short term to the patient benefits), a new approach to applied medicine led by researchers in the universities in alliance with the private sector who carry out clinical studies. Despite the advances of Personalized and Translational Medicine in the developed world in Colombia, this discipline has an incipient development.

Due to its genetic instability, triple-negative breast cancer - (CMTN) (ER-, PR-, Her2 / neu-) among other tumors with a high number of mutations makes it resistant to chemotherapy/radiotherapy regimens generating high morbidity and mortality. Furthermore, genetic instability contributes not only to the immuno-editing of these tumors [5] but to the generation of a suppressive tumor microenvironment [6], which are factors that contribute to the escape of these tumors to their immunosurveillance [7, 8]. However, recent achievements suggest that these factors are controllable using personalized medicine. While immunosuppression is modulated with the use of anti-checkpoint antibodies ("anti-check points" such as anti-CTLA4, anti-PD1, and anti-PDL-1) [9], genetic instability that generates tumor neoantigens, may become the Achilles' heel of these tumors. Phase I clinical studies of patients with melanoma and lung cancer metastatic treated with Ipilimumab (anti-CTLA4 of anti-PD1) - to decrease immunosuppression - using together with vaccines peptides corresponding to tumor mutations that are presented in MHCI and MHCII molecules and are recognized by LT-CD8 as foreign antigens, led these cells to destroy the tumor efficiently when used as a vaccine [10-13]. For this reason, the identification of non-synonymous mutations of single amino acid and vaccination with 25 amino acid peptides incorporating these mutations (synthetic vaccines), is emerging as an alternative for cancer immunotherapy [10-13] in what is called neoantigen based synthetic cancer vaccines. In an approach that takes 16 weeks, today it is possible to go from the analysis of the tumor transcriptome to identify the universe of tumor mutations up to the vaccination of the patient with peptides containing tumor mutations, with the important clinical response to the tumor not achieved so far in patients with melanoma and non-small cell carcinoma of the metastatic lung [10-13]. Therefore, we propose to carry out the first clinical study in Colombia of vaccination of patients with CMTN using synthetic peptides that contain mutations of the tumor itself that will be presented by autologous dendritic cells in order to evaluate the immunogenicity and safety of this type of personalized vaccine. Achieving the specific objectives set out in this project will mean that we have validated in Colombia the experimental design necessary to identify unique epitopes in each tumor of the participants in the study in addition to demonstrating the safety and immunogenicity of these vaccines. Once this has been achieved, we consider having taken an important step towards implementation in our country of the use of this type of vaccine for immunotherapy not only of CMTN but of other highly fatal tumors such as glioblastoma, gastric, esophagus, and pancreas.

This project is carried out by the National University, the Hospital El Tunal de Bogotá, and the Fundación Salud de los Andes, has the collaboration of Professor Luis Fernando Niño and Andrés Pinzón, experts in bioinformatics in the Universidad Nacional; Dr. Chris Miller at Washington University at the McDonnell Genomic Institute at Washington University, School of Medicine in Saint Louis; has the advice of Dr. Pedro Romero from the University of Lausanne (Switzerland) who has extensive experience in immunotherapy clinical trials of melanoma patients with synthetic peptides as a vaccine and with researchers from the Research Group in Immunology and Clinical Oncology (GIIOC) of the Fundación Salud de los Andes.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Cundinamarca
      • Bogota, Cundinamarca, Colombia, 111321
        • Universidad Nacional de Colombia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Be a patient who is prescribed as a treatment for her cancer initiating neo-adjuvant chemotherapy with Doxorubicin / cyclophosphamide (A / C) administered prior to cycles with Taxanes and followed by surgery to remove the tumor.
  • Be between 18 and 75 years old.
  • That the patient agrees to participate in the Clinical Study prior to the start of chemotherapy.
  • Have free venous access.
  • Signature of informed consent.

Exclusion Criteria:

  • Heart disease.
  • Diabetes
  • Renal impairment
  • Coagulation disorders
  • Have been hospitalized in the last month
  • Have another active tumor with the exception of skin tumors of the squamous-cell or basal-cell carcinoma.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neo-antigen pulsed Dendritic cell
Autologous dendritic cells pulsed with tumor-specific neo-antigen (synthetic peptide)
Patients that have already finished their conventional treatment (chemotherapy and/or surgery) will be vaccinated with dendritic cells pulsed with synthetic peptide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse effects and Safety
Time Frame: One year after innoculation
Number of participants with a treatment-related adverse event as associated with dendritic cells and neo-antigen inoculation assessed by CTCAE v4.0
One year after innoculation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neoantigen Immunogenicity
Time Frame: 6 months after last innoculation
Measurement of T cell response against tumor-specific neo-antigen assessed by interferon gamma release by ELISPOT or ELISA of in vitro culture of T cells and mutated peptide-pulsed dendritic cells, normalized against wild type peptide.
6 months after last innoculation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Carlos A Parra-Lopez, MD PhD, Full Professor School of Medicine. Microbiology Department.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2019

Primary Completion (Actual)

December 1, 2020

Study Completion (Actual)

February 1, 2022

Study Registration Dates

First Submitted

September 24, 2019

First Submitted That Met QC Criteria

September 25, 2019

First Posted (Actual)

September 26, 2019

Study Record Updates

Last Update Posted (Actual)

June 21, 2022

Last Update Submitted That Met QC Criteria

June 15, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

We are not going to share individual participant data (IPD)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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