Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04105582 |
| Other study ID # |
TEBICA002 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
August 1, 2019 |
| Est. completion date |
February 1, 2022 |
Study information
| Verified date |
June 2022 |
| Source |
Universidad Nacional de Colombia |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
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.
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.
