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Breast Cancer FemalePhase 1/2TEBICANCT03450044

Immunogenicity and Safety of DCs in Breast Cancer

A Phase 1/2 study testing Dendritic cells in people with Breast Cancer Female, run by Fundación Salud de los Andes at 1 site in Colombia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study aims to evaluate for the first time in Colombia the immunogenicity and safety of autologous DCs as enhancers of the immune response in patients with ductal breast cancer who, prior to surgical resection of the tumor, will receive neo-adjuvant chemotherapy with Doxorubicin and Cyclophosphamide. Read more about this study

Who is it for?
Ages 30 to 65 years, women only
Conditions the study is for
Breast Cancer Female
What is being tested?
Dendritic cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteColombia
Study dates
Jan 2014to Aug 2018
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 65 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Women between 30 and 65 years old.
  • Patients who have histologically confirmed primary invasive ductal carcinoma of the breast.
  • Patients who, at the time of their evaluation, present a breast cancer with TNM classification: IIA, IIB, IIIA, IIIB, IIIC or IV; in whom the breast-tumor relationship is not satisfactory for the surgical procedure, so that they will receive neo-adjuvant chemotherapy with Doxorubicin and Cyclophosphamide for at least 3 cycles.
  • Patients who voluntarily agree to enter the proposed immunotherapy scheme.
  • Absence of second malignant disease with the exception of a cervical carcinoma or a treated basal cell carcinoma.
  • Normal blood, kidney function and hepatic function (neutrophil count 1000 / mm3, lymphocyte count 500 / mm3, hemoglobin 8mg / dl, and platelet count 150,000 / mm3, serum creatinine 1.5mg / dl, BUN 50mg / dl, aminotransferases 2 times of normal value and bilirubin 2.0mg / dl).
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  • Karnofsky higher than 70% or ECOG 0 to 1.
  • Life expectancy greater than three months.
  • Ability to understand informed consent.
  • Have a weight greater than 50 Kilos at the time of apheresis.

Who cannot join

  • Patients who are pregnant or breast-feeding.
  • Patients who have received some type of therapy as treatment for their tumor pathology in the breast, prior to the start of the trial (radiotherapy, chemotherapy, immunotherapy or gene therapy).
  • Metastasis to the central nervous system at the time of inclusion in the study.
  • Active autoimmune disease requiring treatment or history of autoimmune disease, which could be exacerbated by treatment. Patients with endocrine disease controlled by replacement therapy may be included, including thyroid disease, adrenal disease and vitiligo.
  • Presence of a chronic or acute infection, such as HIV, viral hepatitis or tuberculosis, before or after the signing of the informed consent.
  • Use of immunosuppressant within 4 weeks prior to the trial (eg corticosteroids), such as azathioprine, prednisone or cyclosporine A. The use of local steroids (topical, nasal or inhaled) may be acceptable.
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  • Patients with eczema, history of eczema or other eczematous skin disorders or those with acute or chronic exfoliative skin condition (eg atopic dermatitis, burns, impetigo, varicella zoster, severe acne or open wounds).
  • Any disease that could interfere with the patient's ability to carry out the treatment (eg, Crohn's disease, ulcerative colitis or active diverticulitis, severe respiratory, cardiovascular, neurological, infectious disease or uncontrolled metabolic disease), including diseases of the psychiatric type.
  • Clinically significant cardiomyopathy, which requires treatment.
  • Splenectomized patients.
  • Patients who do not receive the neo-adjuvant chemotherapy regimen with Doxorubicin and Cyclophosphamide for three cycles.
  • Patients who have had an excisional biopsy.

Trial locations and contacts

1 site in 1 country.

Colombia1 site

  • Fundación Salud de los Andes

    Bogota, Cundinamarca, 111321

Other trials in Colombia

About this study

Official title: Immunogenicity and Safety of Autologous Dendritic Cells in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy.

This study aims to evaluate for the first time in Colombia the immunogenicity and safety of autologous DCs as enhancers of the immune response in patients with ductal breast cancer who, prior to surgical resection of the tumor, will receive neo-adjuvant chemotherapy with Doxorubicin and Cyclophosphamide. concomitantly with the transfer of autologous DCs. This clinical trial is based on the concept proposed in countries like France more than a decade ago, that chemotherapy or radiotherapy cause the tumor cells to release certain signals that favor the activation of the immune system against cancer. Therefore, the combined use of chemotherapy with vaccination with dendritic cells would provide the immune system with greater antitumor response capacity, taking advantage of the release of said signals to initiate a series of processes that would be reflected in the activation of T lymphocytes capable of destroying the remaining cells of the tumor. To determine the specificity of the response evoked by the adoptive transfer of autologous DCs, in each patient the degree of recognition of the tumor by the immune system before and after said procedure will be evaluated. These results will be compared with those of patients who participated in a control group.

Hypothesis Adoptive transfer of autologous DCs generated in vitro, in patients with stage IIA-IV breast cancer who receive neoadjuvant therapy with Doxorubicin and Cyclophosphamide, is a safe procedure that stimulates anti-tumor immune responses in treated patients.

Read more

Principal aim:

To evaluate the safety and immunogenicity of the use of DCs when used in patients with stage IIA-IV breast cancer in association with neo-adjuvant chemotherapy with Doxorubicin/Cyclophosphamide.

Specific aims:

  • Generate immuno-competent dendritic cells in conditions of Good Clinical Practice and Good Laboratory Practices.
  • Determine in each patient the immunological status of specific T lymphocytes against tumor antigens, before and after chemotherapy, in order to demonstrate whether the adoptive transfer of DCs favors the anti-tumor immune response.
  • Register in patients with breast cancer in neo-adjuvant chemotherapy the class and frequency of adverse effects that could be generated as a result of the adoptive transfer of autologous DCs.
Read the detailed description

The Fundación Salud de los Andes in the framework of a strategic alliance with the National University of Colombia has been working in the planning and development of a clinical trial in Colombia that promotes the search for new therapeutic alternatives for cancer patients. As a translational medicine project, it aims to make the laboratory findings available to the patient. This study explores the combination of immunotherapy (cell therapy) with chemotherapy, in order to obtain better results in the therapeutic management of tumors in patients with breast cancer.

Problem:

Breast cancer is a pathology that in recent years has increased vertiginously its incidence globally. Given the advanced state in which this tumor is usually diagnosed in our environment, the prognosis is seriously compromised, which has led to the current breast cancer represents a major public health problem in Colombia. The established therapies for the management of patients with this type of tumors such as chemotherapy, radio-therapy or surgery, are effective to reduce much of the established tumor mass, but fail to eliminate residual cancer cells, so - often - these treatments cannot prevent the recurrence of the disease. In addition to the above, the quality of life of the patients treated is strongly affected by the toxicity of these treatments on healthy tissues and their undesirable effects, which frequently affects poor adherence to treatment. That is why it is necessary to search for new therapeutic alternatives that are more specific to the tumor and that are better tolerated by patients. Due to the high specificity of the immune system for the recognition of tumors, different modalities of immune therapy for tumor control are currently being explored, which seek to enhance the performance of the patient's defense system so that a cytotoxic and memory response is established against them. tumor cells.

Type of study Clinical Trial Phase I / II.

Methodology:

Patients who attend the consultation due to their mammary pathology for the start of neo-adjuvant chemotherapy will be pre-selected to participate in the study. The participation of the volunteers will be subject to compliance with the inclusion and exclusion criteria defined for the study, as well as the signing of the informed consent. The participants will be randomly distributed into two groups.

PATIENT GROUPS As part of the clinical evaluation at the entrance of the study, a battery of laboratory tests (basic and specific to the trial) will be carried out. Subsequent to the corroboration of compliance with the inclusion criteria, patients will be randomly assigned to one of the two study groups: The first group (A) will be the negative control group, which includes patients who will receive only the standardized chemotherapy treatment for the pathology. The second group (B) will consist of those patients who were randomly selected to receive the adoptive transfer of mature autologous DCs in combination with the neo-adjuvant chemotherapy. In this way, the total of 30 patients will be distributed as follows: 15 patients for group A and 15 patients for group B.

The patients of group B will undergo an apheresis procedure in order to obtain a sample enriched in peripheral blood monocytes from which monocytes will be purified for the production of DCs. The generation of DCs will be carried out under strict conditions of Good Clinical Practices and Good Laboratory Practices.

The adoptive transfer will be carried out concomitantly with the neo-adjuvant chemotherapy treatment (eight and 15 days after chemotherapy dose for a total of 6 injections with autologous DCs).

In the period of application of the doses, a permanent clinical evaluation will be carried out to the patients, to register possible adverse effects (evaluation of the safety of the adoptive transfer of autologous DCs). The effect on the immune response of autologous DCs transferred to patients on chemotherapy vs. the effect on the immune response of chemotherapy without transfer, will be analyzed in each patient before and after chemotherapy using the state of the art of immunological techniques with which will measure the extent of anti-tumor CD8+ T cells expansion (evaluation of the immunogenicity of the adoptive transfer of autologous DCs).

Participating Institutions:

Fundación Salud de los Andes Research Group in Immunology and Clinical Oncology - GIIOC

National University of Colombia - Bogotá. School of Medicine Immunology and Translational Medicine Group Departments of Microbiology and Pathology

Other collaborating institutions:

Clínica del Seno Hospital Universitario Nacional Instituto Nacional de Cancerología Oncocare

Being tested
Dendritic cells
Keywords
Chemotherapy, Breast Cancer, Dendritic cells, Immunotherapy, Doxorubicine
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dendritic cellsBiological

    Adoptive transfer of autologous DCs

Study groups in NCT03450044
Study groupRoleWhat they receive
VaccinatedExperimentalTransfer of autologous dendritic cells interspersed with chemotherapy doses
Receives: Biological: Dendritic cells
ControlNo interventionControl patients who follow their basic treatment with chemotherapy with the A/C scheme

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse effects

    Number of participants with treatment-related adverse events as associated with DCs inoculation assessed by CTCAE v4.0

    Measured: One year after innoculation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Mar 2018
  2. Study startJan 2014
  3. Primary completionJul 2018
  4. Study completionAug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03450044
Sponsor's protocol ID
TEBICA-001
Acronym
TEBICA
Status last verified
Feb 2020
First submitted
12 Feb 2018
Last updated
5 Feb 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K. Immunobiology of dendritic cells. Annu Rev Immunol. 2000;18:767-811. doi: 10.1146/annurev.immunol.18.1.767.

    PubMed 10837075

  • Banchereau J, Palucka AK. Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol. 2005 Apr;5(4):296-306. doi: 10.1038/nri1592.

    PubMed 15803149

  • Brossart P, Wirths S, Brugger W, Kanz L. Dendritic cells in cancer vaccines. Exp Hematol. 2001 Nov;29(11):1247-55. doi: 10.1016/s0301-472x(01)00730-5.

    PubMed 11698120

  • Butterfield LH, Ribas A, Dissette VB, Amarnani SN, Vu HT, Oseguera D, Wang HJ, Elashoff RM, McBride WH, Mukherji B, Cochran AJ, Glaspy JA, Economou JS. Determinant spreading associated with clinical response in dendritic cell-based immunotherapy for malignant melanoma. Clin Cancer Res. 2003 Mar;9(3):998-1008.

    PubMed 12631598

  • Chaput N, De Botton S, Obeid M, Apetoh L, Ghiringhelli F, Panaretakis T, Flament C, Zitvogel L, Kroemer G. Molecular determinants of immunogenic cell death: surface exposure of calreticulin makes the difference. J Mol Med (Berl). 2007 Oct;85(10):1069-76. doi: 10.1007/s00109-007-0214-1. Epub 2007 May 22.

    PubMed 17891368

  • Dauer M, Schad K, Herten J, Junkmann J, Bauer C, Kiefl R, Endres S, Eigler A. FastDC derived from human monocytes within 48 h effectively prime tumor antigen-specific cytotoxic T cells. J Immunol Methods. 2005 Jul;302(1-2):145-55. doi: 10.1016/j.jim.2005.05.010.

    PubMed 15992809

  • Dong Xda E, Ito N, Lotze MT, Demarco RA, Popovic P, Shand SH, Watkins S, Winikoff S, Brown CK, Bartlett DL, Zeh HJ 3rd. High mobility group box I (HMGB1) release from tumor cells after treatment: implications for development of targeted chemoimmunotherapy. J Immunother. 2007 Sep;30(6):596-606. doi: 10.1097/CJI.0b013e31804efc76.

    PubMed 17667523

  • Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way. Nat Med. 2004 May;10(5):475-80. doi: 10.1038/nm1039.

    PubMed 15122249

  • Gabrilovich D. Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol. 2004 Dec;4(12):941-52. doi: 10.1038/nri1498.

    PubMed 15573129

  • Kalinski P, Okada H. Polarized dendritic cells as cancer vaccines: directing effector-type T cells to tumors. Semin Immunol. 2010 Jun;22(3):173-82. doi: 10.1016/j.smim.2010.03.002. Epub 2010 Apr 20.

    PubMed 20409732

  • Mailliard RB, Wankowicz-Kalinska A, Cai Q, Wesa A, Hilkens CM, Kapsenberg ML, Kirkwood JM, Storkus WJ, Kalinski P. alpha-type-1 polarized dendritic cells: a novel immunization tool with optimized CTL-inducing activity. Cancer Res. 2004 Sep 1;64(17):5934-7. doi: 10.1158/0008-5472.CAN-04-1261.

    PubMed 15342370

  • Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Metivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007 Jan;13(1):54-61. doi: 10.1038/nm1523. Epub 2006 Dec 24.

    PubMed 17187072

  • Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, Mintz AH, Engh JA, Bartlett DL, Brown CK, Zeh H, Holtzman MP, Reinhart TA, Whiteside TL, Butterfield LH, Hamilton RL, Potter DM, Pollack IF, Salazar AM, Lieberman FS. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with alpha-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol. 2011 Jan 20;29(3):330-6. doi: 10.1200/JCO.2010.30.7744. Epub 2010 Dec 13.

    PubMed 21149657

  • Pinzon-Charry A, Maxwell T, Lopez JA. Dendritic cell dysfunction in cancer: a mechanism for immunosuppression. Immunol Cell Biol. 2005 Oct;83(5):451-61. doi: 10.1111/j.1440-1711.2005.01371.x.

    PubMed 16174093

  • Ramakrishnan R, Antonia S, Gabrilovich DI. Combined modality immunotherapy and chemotherapy: a new perspective. Cancer Immunol Immunother. 2008 Oct;57(10):1523-9. doi: 10.1007/s00262-008-0531-4. Epub 2008 May 17.

    PubMed 18488219

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dendritic cells in people with Breast Cancer Female, run by Fundación Salud de los Andes at 1 site in Colombia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse effects (time frame: One year after innoculation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03450044, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2020.

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