Clinical trial NCT05204199: Role of Microbiome in BCG Responsiveness Prediction
Official title: Towards Individualization of Bladder Cancer Therapy: the Role of Microbiome in BCG Responsiveness Prediction
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Microbiome
Bladder Cancer
Keywords: BCG
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Krebsliga Schweiz
First posted: 2022-01-24
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Difference in microbial Profile
timeFrame: 1 year
Secondary outcomes:
measure: Biobank
timeFrame: 1 year
Other outcomes:
Locations:
city: Baden
country: Switzerland
facility: Kantonsspital Baden
state: Aargau
city: Biel
country: Switzerland
facility: Spitalzentrum Biel
state: Bern
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
state: Saint Gallen
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
state: Zürich
city: Zürich
country: Switzerland
facility: University Hospital Zürich
Study officials:
affiliation: University Hospital Zurich, Departement of Urology
name: Cédric Poyed, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.