Using metformin to treat non-muscle-invasive bladder cancer

Phase II Study of Oral Metformin for Intravesical Treatment of Non-muscle-invasive Bladder Cancer

This study tests if the diabetes drug metformin can help treat low-grade non-muscle-invasive bladder cancer in patients by seeing how well it works over three months.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 49 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 3 sites (Nijmegen, Gelderland and 2 other locations)
• Trial ID: NCT03379909 on ClinicalTrials.gov

What this trial studies

This phase II clinical study evaluates the effectiveness of oral metformin in treating low-grade non-muscle-invasive bladder cancer (NMIBC) in up to 49 patients. Participants will take metformin at doses up to 1500 mg twice daily for three months, after which their response will be assessed through a transurethral resection of the bladder tumor. The study focuses on an index lesion measuring between 0.5 and 1.0 cm, with the aim of determining the overall response to the treatment. The study is conducted across multiple centers in the Netherlands.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with low-grade NMIBC and specific tumor characteristics.

Not a fit: Patients with high-grade tumors or those with positive cytology may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could provide a new, effective option for patients with low-grade NMIBC.

How similar studies have performed: While the use of metformin in cancer treatment is being explored, this specific approach for NMIBC is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Age \> 18 years.
* Patients with primary or recurrent suspectedTa or T1, G1 or G2 (low grade) urothelial carcinoma of the bladder with no suspicion of carcinoma in situ.
* Patients must have at least 1 lesion but no more than 5.
* There must be one index lesion measuring between 0.5 and 1.0 cm in its greatest dimension.
* Bimanual examination immediately following cystoscopyshould be carried out and no mass should be felt.
* Adequate renal function (eGFR \>50 ml/min/1.73m2 according to CKD-EPI). (47)
* Adequate liver function (bilirubin \<1.5 times upper limit of normal, ALAT or ASAT \<2.5 the upper limit of normal).
* Eligible patients must be fully informed of the investigational nature of the study and written signed informed consent must be obtained prior to any study specific investigations.
* Mentally, physically, and geographically able to undergo treatment and follow up.

Exclusion Criteria:

* Patients with positive cytology (suspected for high-grade urothelial carcinoma, TPS 4 or TPS 5) or suspected grade 3 tumours.
* Patients with diabetes mellitus receiving metformin or having received metformin in the past 6 months.
* Patients who have received intravesical treatment (chemotherapy or immunotherapy) within the last 3 months.
* Patients that are currently receiving other anti-cancer therapy.
* Patients with existing urinary tract infection or recurrent severe bacterial cystitis.
* Patients that need to be treated with a transurethral catheter.
* Patients with urogenital tumours with histology other than urothelial carcinoma (i.e. squamous cell or adenocarcinoma) or with urothelial carcinoma involving the upper tract or the prostatic urethra.
* Patients with a history of other primary malignancy (other than squamous or basal cell skin cancers or cone biopsied CIS of the uterine cervix or prostate carcinoma treated curatively with normal PSA values at inclusion) in the last five years.
* Patients with active, uncontrolled impairment of the renal, hepatobiliary, cardiovascular, gastrointestinal, urogenital, neurologic or hematopoietic systems that, in the opinion of the investigator, would predispose to the development of complications from the administration of metformin.
* Patients who are using loop diuretics, cimetidine, ranitidine, cetirizine, trimethoprim, vandetanib, kinidine and/or HIV medication, for which no reasonable alternative is available.
* Women who are pregnant or lactating. Individuals of reproductive potential may not participate unless agreeing to use an effective contraceptive method for themselves and/or their sexual partner.
* Patients with ECOG-WHO performance status of 3 or 4.
* Patients with a known history of alcohol abuse.
* Patients with a known hypersensitivity to metformin.
* Patients who in the investigator's opinion, cannot comply with provisions of the protocol or do not understand the nature of the study.

Where this trial is running

Nijmegen, Gelderland and 2 other locations

• RadboudUMC — Nijmegen, Gelderland, Netherlands (Not_yet_recruiting)
• Sint Franciscus Gasthuis — Rotterdam, South Holland, Netherlands (Not_yet_recruiting)
• Academic Medical Center — Amsterdam, Netherlands (Recruiting)

Study contacts

• Study coordinator: M. J. Remmelink, MD

Conditions Superficial Bladder Cancer; Bladder Cancer; metformin; marker lesion