Immunological Response of Bladder Cancer Patients Under BCG (IMMUNOBCG)

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

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.

Study Overview

• Status: Suspended
• Conditions: Bladder Cancer; Bacillus Calmette-Guerin
• Intervention / Treatment: Biological: Bacillus Calmette Guerin; Other: PLACEBO

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Campinas, SP, Brazil, 13034685
      • Pontifical Catholic University of Campinas Hospital
    • Campinas, SP, Brazil, 13083887
      • Hospital das Clínicas Unicamp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• NMIBC with the indication for intravesical BCG treatment;

Exclusion Criteria:

• Previous BCG treatment;
• Muscle invasive tumor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	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 Names: BCG
Placebo Comparator: Placebo; Placebo group (n = 16): 0.9% saline solution in the same volume as BCG vaccine in a single dose.	Other: PLACEBO; 0.1 ml 0.9% saline in the same volume as the BCG vaccine in a single dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow Cytometry	Cellular Immune Response	Day 0
Flow Cytometry	Cellular Immune Response	Day 14
Flow Cytometry	Cellular Immune Response	Day 21
Flow Cytometry	Cellular Immune Response	Day 35
Flow Cytometry	Cellular Immune Response	Day 49
Flow Cytometry	Cellular Immune Response	Day 180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: University of Campinas, Brazil
• Collaborators: Coordination for the Improvement of Higher Education Personnel; Pontifical University Catholic of Campinas
• Investigators: Principal Investigator: Leonardo O Reis, MD, PhD, University of Campinas

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): February 3, 2025
• Primary Completion (Estimated): December 18, 2026
• Study Completion (Estimated): December 22, 2028

Study Registration Dates

• First Submitted: March 12, 2021
• First Submitted That Met QC Criteria: March 16, 2021
• First Posted (Actual): March 19, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Bladder cancer; Immunotherapy; BCG
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; BCG Vaccine
• Other Study ID Numbers: BCG IMMUNO Bladder

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No