Clinical trial NCT03379909: Phase II Study of Oral Metformin for Intravesical Treatment of Non-muscle-invasive Bladder Cancer
Official title: Phase II Study of Oral Metformin for Intravesical Treatment of Non-muscle-invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Superficial Bladder Cancer
Bladder Cancer
Keywords: metformin
marker lesion
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
First posted: 2017-12-20
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A multi-center, open-label, phase II clinical study of metformin in up to evaluable 49 patients with low-grade NMIBC with the aim to determine the overall response to administration of oral metformin for 3 months in a index papillary NMIBC tumour.

Detailed description: A multi-center, open-label, phase II clinical study of metformin in up to 49 patients with low-grade NMIBC with the aim to determine the overall response to administration of oral metformin for 3 months in a index tumour (0.5-1 cm) selected ane measured during cystoscopy. All patients will receive metformin orally at doses up to 1500 mg twice daily. Metformin treatment will start directly after informed consent is obtained. After 3 months of metformin treatment, the effect of metformin on the index lesion is evaluated by performing a transurethral resection of the bladder tumour under anaesthesia. Residual tumour, if present at this evaluation, will be resected. In case of complete disappearance of the index lesion the former tumour area will be biopsied.

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.

Primary outcomes:
measure: Overall response
timeFrame: 3 months
Secondary outcomes:
measure: Time to recurrence
timeFrame: 5 years
measure: Toxicity of metformin treatment
timeFrame: 3 months
measure: Partial response
timeFrame: 3 months.
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: RadboudUMC
state: Gelderland
city: Rotterdam
country: Netherlands
facility: Sint Franciscus Gasthuis
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
Study officials:
References:
citation: Molenaar RJ, van Hattum JW, Brummelhuis IS, Oddens JR, Savci-Heijink CD, Boeve ER, van der Meer SA, Witjes JF, Pollak MN, de Reijke TM, Wilmink JW. Study protocol of a phase II clinical trial of oral metformin for the intravesical treatment of non-muscle invasive bladder cancer. BMC Cancer. 2019 Nov 21;19(1):1133. doi: 10.1186/s12885-019-6346-1.