Role of Microbiome in BCG Responsiveness Prediction (SILENTEMPIRE)

Towards Individualization of Bladder Cancer Therapy: the Role of Microbiome in BCG Responsiveness Prediction

Our primary aim is to investigate the use of microbial profile from the bladder and the feces of NMIBC patients as a predicting tool for therapy response prior to BCG administration.

Our second aim is to collect additional samples (blood, instrumented urine, bladder tissue, feces) to establish a local biobank for future microbiome projects.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer; Microbiome

Detailed Description

The microbiome, defined as a characteristic microbial community occupying a reasonably well-defined environment (e.g. gut microbiome), has been increasingly linked with different medical conditions and also with cancer. While there have been numerous investigations into the gut bacterial ecosystem, scientists have started to pay attention to the microbiome of the bladder only recently. Results from newest investigations support the understanding that the bladder possesses its own microbiome and it is not germ-free. Studying the relationship between bladder cancer and bladder and gut microbiome may lead to new insights which can be used to predict tumor behavior and/or response to therapy.

With this project, we aim to investigate the use of microbial fingerprint from the bladder and from the feces of bladder cancer patients in predicting therapy response prior to administration of Bacillus Calmette-Guerin or BCG. BCG causes the body's own immune system to attack the bladder cancer cells. It is applied directly into the bladder to prevent the cancer from growing and from regrowing. However, in around 40% of patients this treatment is not successful, BCG should be avoided, and other therapy strategies should be chosen. Unfortunately, there is no test available yet, which help to select patients who will benefit from the therapy before the therapy is started.

In this project we intend to determine the microbial fingerprint and to analyze if this fingerprint can be used as a selection tool. This tool may enable as us in the future to avoid application of BCG therapy for patient with a high risk of therapy failure and save time to start alternative therapy options and hopefully avoid tumor progression. Our second aim is to collect additional samples (blood, instrumented urine, bladder tissue, feces) to establish a local biobank for future microbiome projects.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Uwe Bieri, MD; Phone Number: +41792998114; Email: uwe.bieri@usz.ch

Study Locations

• Switzerland
  • Zürich, Switzerland, 8091
    • Recruiting
    • University Hospital Zurich
    • Contact: Cédric Poyet, MD; Phone Number: 0041 44 255 11 11; Email: cedric.poyet@usz.ch
    • Sub-Investigator: Uwe Bieri, MD
    • Sub-Investigator: Silvan Sigg, MD
  • Aargau
    • Baden, Aargau, Switzerland, 5404
      • Recruiting
      • Kantonsspital Baden
      • Principal Investigator: Lukas J. Hefermehl, MD
      • Contact: Lukas J. Hefermehl, MD; Email: lukas.hefermehl@ksb.ch
  • Bern
    • Biel, Bern, Switzerland, 2501
      • Not yet recruiting
      • Spitalzentrum Biel
      • Contact: Roland Seiler-Blarer, Prof.; Email: roland.seiler-blarer@szb-chb.ch
      • Principal Investigator: Roland Seiler-Blarer, Prof.
  • Saint Gallen
    • St. Gallen, Saint Gallen, Switzerland, 9007
      • Recruiting
      • Kantonsspital St. Gallen
      • Contact: Daniel Engeler, MD; Email: daniel.engeler@kssg.ch
      • Principal Investigator: Daniel Engeler, MD
  • Zürich
    • Winterthur, Zürich, Switzerland, 8401
      • Recruiting
      • Kantonsspital Winterthur
      • Contact: Beat Förster, MD; Email: beat.foerster@ksw.ch
      • Principal Investigator: Beat Förster, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Group A: Patients without a urological or gastrointestinal malignancy undergoing non-oncological bladder surgery or transurethral resection of the prostate (TUR-P) fulfilling the following criteria. At the time of study inclusion, no urological symptoms or relevant urological disease (Unclear Macrohematuria, Cystolithiasis, prostate Cancer )

Group B: Low Risk NMIBC (primary, solitary, Ta / low grad < 3cm, no carcinoma in situ (CIS)).

Group C: NMIBC patients, BCG candidates, assessed as intermediate (between the category of low- and high risk) or high risk (T1 or high grade or CIS or multiple, recurrent and large (> 3 cm) Ta/ low grade tumours).

Description

Inclusion Criteria

• Signed informed consent
• Ability to understand and follow study procedures and understand informed consent
• age 18 - 90 years

Exclusion Criteria

• Antibiotic treatment within the last month
• Immuno-/chemotherapy within the past 6 months
• Immunosuppressive therapy
• Major medical, neoplastic (with the exception of skin cancer), surgical or psychiatric condition requiring ongoing management. Minor, well-controlled conditions, such as medically controlled arterial hypertension or occupational asthma, may be present.
• Additional major diagnosis known to affect the gut or bladder microbiota (e. g. liver cirrhosis, systemic sclerosis, inflammatory bowel disease, inflammatory bowel syndrome, celiac disease, neuropathic bladder)
• Major past intestinal surgery, especially in small intestine or colon. Cholecystectomy, appendectomy, past perianal surgery or past hernia repair may be present.
• Major gastrointestinal symptoms (diarrhoea, constipation, abdominal pain, vomiting, unexplained weight loss, rectal bleeding or blood in the stool)
• Bladder augmentation surgery.
• Indwelling urinary catheter

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group A; Patients without a urological or gastrointestinal malignancy undergoing non-oncological bladder surgery or transurethral resection of the prostate (TUR-P)
Group B; Low Risk NMIBC (primary, solitary, Ta / low grad < 3cm, no carcinoma in situ (CIS))
Group C; NMIBC patients, BCG candidates, assessed as intermediate (between the category of low- and high risk) or high risk (T1 or high grade or CIS or multiple, recurrent and large (> 3 cm) Ta/ low grade tumours).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in microbial Profile	use of microbial profile from the bladder and the feces of NMIBC patients as a potential binary classification system, to substratify BCG-candidates into "anticipated BCG-responder (aBCGr)" and "anticipated BCG-non-responder (aBCGnr)" groups in predicting therapy response prior to BCG administration.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biobank	collect additional samples (blood, instrumented urine, bladder tissue, feces) to establish a local biobank for future microbiome projects	1 year

Collaborators and Investigators

• Sponsor: Cédric Poyet
• Collaborators: Krebsliga Schweiz
• Investigators: Principal Investigator: Cédric Poyed, MD, University Hospital Zurich, Departement of Urology

Publications and helpful links

General Publications

• Bieri U, Scharl M, Sigg S, Szczerba BM, Morsy Y, Ruschoff JH, Schraml PH, Krauthammer M, Hefermehl LJ, Eberli D, Poyet C. Prospective observational study of the role of the microbiome in BCG responsiveness prediction (SILENT-EMPIRE): a study protocol. BMJ Open. 2022 Apr 18;12(4):e061421. doi: 10.1136/bmjopen-2022-061421.

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2022
• Primary Completion (Estimated): October 20, 2025
• Study Completion (Estimated): October 20, 2025

Study Registration Dates

• First Submitted: December 29, 2021
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: 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
• Other Study ID Numbers: 2021-01783

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