Immunological Response of Bladder Cancer Patients Under BCG

Bladder Cancer Clinical Trial

— IMMUNOBCG  

Official title:

Systemic Immunological Response of Bladder Cancer Patients Under Bacillus Calmette Guérin Treatment

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04806178
• Other study ID #: BCG IMMUNO Bladder
• Status: Suspended
• Phase: Phase 3
• Start date: February 3, 2025
• Est. completion date: December 22, 2028

Study information

• Verified date: April 2024
• Source: University of Campinas, Brazil
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 30
• Est. completion date: December 22, 2028
• Est. primary completion date: December 18, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• NMIBC with the indication for intravesical BCG treatment;

Exclusion Criteria:

• Previous BCG treatment;

• Muscle invasive tumor.

Related Conditions & MeSH terms

• Bacillus Calmette-Guerin
• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Biological:
• 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.

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

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas Unicamp	Campinas	SP
Brazil	Pontifical Catholic University of Campinas Hospital	Campinas	SP

Sponsors (3)

Lead Sponsor	Collaborator
University of Campinas, Brazil	Coordination for the Improvement of Higher Education Personnel, Pontifical University Catholic of Campinas

Country where clinical trial is conducted

Brazil, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Flow Cytometry	Cellular Immune Response	Day 0
Primary	Flow Cytometry	Cellular Immune Response	Day 14
Primary	Flow Cytometry	Cellular Immune Response	Day 21
Primary	Flow Cytometry	Cellular Immune Response	Day 35
Primary	Flow Cytometry	Cellular Immune Response	Day 49
Primary	Flow Cytometry	Cellular Immune Response	Day 180
Secondary	Adverse Effects and Change from Baseline Voiding Symptoms	American Urological Association Symptom Score Questionnaire - minimum 0 and maximum 35, higher scores mean a worse outcome.	Day 21
Secondary	Adverse Effects and Change from Baseline Voiding Symptoms	American Urological Association Symptom Score Questionnaire - minimum 0 and maximum 35, higher scores mean a worse outcome.	Day 35
Secondary	Adverse Effects and Change from Baseline Voiding Symptoms	American Urological Association Symptom Score Questionnaire - minimum 0 and maximum 35, higher scores mean a worse outcome.	Day 49