Personalized Vaccine for Cancer Immunotherapy

NCT04879888 | Completed Phase 1 DMC

• 1 other identifier: VP-CMTN-UN-2017
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Due to their genetic instability, breast tumors that do not express receptors for Estrogens, Progestagens or amplify the Her2 / neu oncogene \[called triple-negative breast cancer (TNTC)\] and other tumors such as melanoma, non-small cell lung cancer, accumulate numerous mutations that make them highly resistant to different regimens of chemo- or radiotherapy, thereby generating high morbidity and mortality. However, immunology can turn the genetic instability of tumors into the Achilles' tendon. Evidence of this has been revealed in Phase I clinical studies in patients with melanoma and lung cancer in an advanced stage of metastasis treated with Ipilimumab (anti-CTLA4) to decrease immunosuppression, in whom peptides containing mutations presented in Major Complex molecules Histocompatibility of Class I (HCM I) of the tumor itself results in their recognition as "foreign" neo-antigens leading to the efficient destruction of the tumor by anti-tumor CD8 + T lymphocytes that are amplified when they are vaccinated with these peptides. For this reason, the identification of non-synonymous mutations of single amino acid and vaccination with 25 amino acid peptides that incorporate these mutations (synthetic vaccines) is emerging today as an alternative for immunotherapy of cancers responsible for high mortality in humans. In an approach that takes 16 weeks, today, it is possible to go from the analysis of the tumor's transcriptome (which allows identifying the universe of tumor mutations) to the patient's vaccination with a personalized vaccine that contains neo-antigens of his tumor. TNBC is the most aggressive breast tumor, representing around 25% of breast cancers in our environment. While generally, at least 30% of women with other types of metastatic breast cancer survive 5 years after diagnosis, most patients diagnosed with metastatic CMTN die within this time. The lack of selective therapies and the poor prognosis of patients with NTMC make their therapeutic management difficult, so the implementation of new therapies for this type of tumor is the main focus of researchers who seek more effective and selective treatments to improve the life expectancy of patients without compromising their quality of life. The genetic instability and high rate of mutations of the TNBC most likely favor the generation of neo-epitopes. Still, due to the immunosuppressive environment of the tumor, it escapes the immunosurveillance of the immune system. Despite the high mortality induced by this tumor, a percentage of patients treated with neoadjuvant chemotherapy with agents such as Doxorubicin and Cyclophosphamide (AC) + Taxanes respond to this chemotherapy regimen. In particular, the anti-tumor effect of AC is attributed to two things: (i) the direct cytotoxic effect on the tumor cell, (ii) the immunostimulation of T lymphocytes promoted by Immunogenic Cell Death (ICM) selectively induced by these drugs. Therefore, in this project, we propose to carry out the first clinical study in Colombia of vaccination of patients with TNBC with synthetic peptides that contain mutations of their own tumor to evaluate the immunogenicity and safety of this type of personalized vaccine as a therapeutic alternative for this tumor. Achieving the specific objectives set out in this project would mean that we have been validated in Colombia the experimental design necessary to identify unique epitopes in tumors and demonstrate the safety and immunogenicity of these vaccines. We consider that having achieved the above; we will have taken an important step towards the implementation in our country of the use of this type of vaccine for immunotherapy not only of TNBC but of other tumors such as glioblastoma, gastric, esophagus, and pancreas, highly fatal due to its high mutation rate.

Conditions

Breast Cancer Female

Keywords

Triple negative breast cancer; Neo-adjuvant chemotherapy; Dendritic cells; Peptide; Immunotherapy; Immune-monitoring; Personalized vaccines

Outcome Measures

Primary Outcomes (1)

• Number of adverse effects

  Evaluation of number and severity of the adverse effects in the vaccinated patients

  From day 0 (vaccination 1) until 1 month after last vaccination

Study Arms (1)

Vacuna

EXPERIMENTAL

Triple-negative breast cancer patients with specific tumor mutation, with six doses of peptide-pulsed autologous dendritic cells after surgery.

Biological: Peptide pulsed Dendritic cell

Interventions

Peptide pulsed Dendritic cell BIOLOGICAL

Intradermal vaccination with peptide-pulsed autologous dendritic cells in 200 µL of patient's serum in six doses weekly after surgery.

Vacuna

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a diagnosis of ductal cancer who enter the primary or neoadjuvant chemotherapy regimen treated with Doxorubicin or Cyclophosphamide.
• Patients with breast cancer with the HLA-A \* 02: 01 haplotype.
• Women of legal age who are not pregnant or breastfeeding (patients or controls).
• Patients who have histologically confirmed primary breast carcinoma of the ductal type.
• Karnofsky index greater than 70%
• Voluntary acceptance of informed consent.

You may not qualify if:

• Patients with a diagnosis of triple-negative breast cancer.
• Pregnant patients
• Patients under age or over 70 years
• Patients diagnosed with autoimmune diseases
• The patient has a Karnofsky lower than 70% or an ECOG higher than 1.
• Patients who have received some therapy as a treatment for their tumor pathology (radiotherapy, chemotherapy, immunotherapy, or gene therapy).
• Active autoimmune disease requiring treatment or a history of autoimmune disease that could be exacerbated by treatment. Patients with endocrine disease controlled by replacement therapy, including thyroid disease, adrenal disease, and vitiligo, can be included.
• Presence of a chronic or acute infection, such as HIV, viral hepatitis, or tuberculosis, before or after signing the informed consent.
• Use of immunosuppressants within 4 weeks before the trial (e.g., corticosteroids), such as azathioprine, prednisone, or cyclosporine A. The use of local steroids (topical, nasal, or inhaled) may be acceptable.
• Clinically significant cardiomyopathy, which requires treatment.
• Splenectomized patients.
• Patients who do not receive the neoadjuvant chemotherapy regimen with Doxorubicin and cyclophosphamide for three cycles or receive some other type of complementary therapy such as taxanes.

Sponsors & Collaborators

• Universidad Nacional de Colombia: lead
• Fundación Salud de los Andes: collaborator
• Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología (COLCIENCIAS): collaborator
• Subred Integrada de Servicios de Salud Sur ESE - Colombia (South America): collaborator

Study Sites (1)

Facultad de Medicina - Universidad Nacional de Colombia

Bogota, Cundinamarca, 111321, Colombia

Location

Related Publications (1)

• Bernal-Estevez D, Sanchez R, Tejada RE, Parra-Lopez C. Chemotherapy and radiation therapy elicits tumor specific T cell responses in a breast cancer patient. BMC Cancer. 2016 Aug 3;16:591. doi: 10.1186/s12885-016-2625-2.

  PMID: 27484900 RESULT

Related Links

• Dendritic cell generation

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Carlos A Parra-López, MD, PhD

  Full time professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: April 30, 2021
• First Posted: May 10, 2021
• Study Start: August 1, 2016
• Primary Completion: December 30, 2016
• Study Completion: July 30, 2017
• Last Updated: May 10, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CO (1)