Immunological Response of Bladder Cancer Patients Under BCG

NCT ID: NCT04806178

Last Updated: 2024-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-03

Study Completion Date

2024-08-18

Brief Summary

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Bladder cancer (BC) is one of the most common cancers worldwide and the most successful example of vaccine in cancer treatment, representing an efficient model for studying the importance of systemic and local immune mechanisms. Despite being the standard of treatment for the last 40 years, the exact mode of action of immunotherapy with the bacillus Calmette-Guérin (BCG) is still poorly defined. In a mechanistic study, the investigators intend to prospectively investigate immunological signatures, including immune-checkpoints, pre and post-treatment in patients with BC, and correlate the cytokines of the immune by-product and BCG administration pathway to understand the independent contributions of BCG priming (prior exposure to BCG) and crosstalk immunotherapy between tumor profiles and immune response of the patient. The proposed research strategy is justified by the need to identify subsets of patients who better respond to an intervention, or to predict why new immunotherapies and drugs may be successful or failed in clinical trials.

Detailed Description

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Recognizing patient-to-patient variability, key data scarcity, and insight into traditional reductionist therapy, the BCG model offers exceptionally compelling opportunities to understand how immune system behavior in health and disease emerges from local, systemic, genetic, epigenetic, cellular, and environmental modulating factors.

The application seeks to change the current clinical practice and research paradigms, by using new theoretical concepts, challenging bladder cancer patients with a highly effective, safe, and affordable immunotherapy, the gold standard in the last 40 years of NMIBC, and in light of new concepts and methodologies brought by the paradigm of immune-checkpoint inhibitors that justified the Nobel Prize in Physiology or Medicine in 2018.

The current proposal has the potential to impact the prognosis and identification of those who are unlikely to respond to immune-checkpoint inhibitors, scenarios in which important unanswered questions remain, particularly as this class of agents advances along the spectrum of non-metastatic disease.

In a mechanistic approach, patients diagnosed with NMIBC and with the indication for intravesical BCG treatment will be randomized to placebo versus a priming intradermic BCG 14 days before the intravesical treatment and followed up to 180 days.

The investigators will define important clinical paradigms:

1. The role of the priming effect on the immune system and better understanding of BCG immunotherapy, with a clear potential for improvement of bladder cancer treatment in NMIBC and MIBC scenarios;
2. The potential of BCG, a widely used vaccine, to improve or impair the results of new immunotherapies, given its long-lasting effect;
3. Rational to develop future treatment associations of BCG and immune-checkpoints. \\

Under the new immunological concepts, a better understanding of tumor-associated immune responses in BC patients could provide more informed clinical decisions and treatment optimization.

Considering the growing need of assessing the value of treatment at the expense of cost, part of our proposal strategy is to limit financial toxicity as an important issue in cancer treatment and new immunotherapies.

Conditions

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Bladder Cancer Bacillus Calmette-Guerin

Keywords

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BCG Bladder cancer Immunotherapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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BCG intradermal vaccine

Intradermal BCG Group (n=16): 0.1 ml of lyophilized, live, and attenuated BCG intradermal vaccine, containing between 2 and 8 x 1.000.000 C.F.U in a single dose.

Group Type ACTIVE_COMPARATOR

Bacillus Calmette Guerin

Intervention Type BIOLOGICAL

0.1 ml of lyophilized, live, and attenuated BCG intradermal vaccine, containing between 2 and 8 x 1.000.000 C.F.U in a single dose.

Placebo

Placebo group (n = 16): 0.9% saline solution in the same volume as BCG vaccine in a single dose.

Group Type PLACEBO_COMPARATOR

PLACEBO

Intervention Type OTHER

0.1 ml 0.9% saline in the same volume as the BCG vaccine in a single dose.

Interventions

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Bacillus Calmette Guerin

0.1 ml of lyophilized, live, and attenuated BCG intradermal vaccine, containing between 2 and 8 x 1.000.000 C.F.U in a single dose.

Intervention Type BIOLOGICAL

PLACEBO

0.1 ml 0.9% saline in the same volume as the BCG vaccine in a single dose.

Intervention Type OTHER

Other Intervention Names

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BCG

Eligibility Criteria

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Inclusion Criteria

* NMIBC with the indication for intravesical BCG treatment;

Exclusion Criteria

* Previous BCG treatment;
* Muscle invasive tumor.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Coordination for the Improvement of Higher Education Personnel

OTHER

Sponsor Role collaborator

Pontifical University Catholic of Campinas

OTHER

Sponsor Role collaborator

University of Campinas, Brazil

OTHER

Sponsor Role lead

Responsible Party

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Leonardo Oliveira Reis

Professor Livre Docente

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Leonardo O Reis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Campinas

Locations

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Pontifical Catholic University of Campinas Hospital

Campinas, São Paulo, Brazil

Site Status

Hospital das Clínicas Unicamp

Campinas, São Paulo, Brazil

Site Status

Countries

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Brazil

References

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Ji N, Mukherjee N, Morales EE, Tomasini ME, Hurez V, Curiel TJ, Abate G, Hoft DF, Zhao XR, Gelfond J, Maiti S, Cooper LJN, Svatek RS. Percutaneous BCG enhances innate effector antitumor cytotoxicity during treatment of bladder cancer: a translational clinical trial. Oncoimmunology. 2019 May 25;8(8):1614857. doi: 10.1080/2162402X.2019.1614857. eCollection 2019.

Reference Type BACKGROUND
PMID: 31413921 (View on PubMed)

van Puffelen JH, Keating ST, Oosterwijk E, van der Heijden AG, Netea MG, Joosten LAB, Vermeulen SH. Trained immunity as a molecular mechanism for BCG immunotherapy in bladder cancer. Nat Rev Urol. 2020 Sep;17(9):513-525. doi: 10.1038/s41585-020-0346-4. Epub 2020 Jul 16.

Reference Type BACKGROUND
PMID: 32678343 (View on PubMed)

Other Identifiers

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BCG IMMUNO Bladder

Identifier Type: -

Identifier Source: org_study_id