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RecruitingNCT03379909TROJANUpdated Sep 21, 2023

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

A Phase 2 interventional study of Metformin in Superficial Bladder Cancer and Bladder Cancer, sponsored by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA). Recruiting at 3 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-09-21.

Sponsored by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Primary completion was expected by Jul 2024, 2 years 2 months ago, but the record still lists the study as recruiting.
  • Started Sep 2019; still recruiting 7 years 1 month later.
Phase
Phase 2
Study type
Interventional
Enrollment
49
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Superficial Bladder Cancer
  • Bladder Cancer

Keywords

  • metformin
  • marker lesion
03

In context

Non-Muscle Invasive Bladder Neoplasms

272 studies on the registry are indexed under Non-Muscle Invasive Bladder Neoplasms; 116 are open to participants now.

This study's planned enrollment of 49 is below the median of 69 across 210 interventional studies indexed under Non-Muscle Invasive Bladder Neoplasms.

Browse Non-Muscle Invasive Bladder Neoplasms studies →

Lead sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) is the lead sponsor of 532 studies on the registry; 185 are open to participants now.

Browse Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
49 participants (estimated)

Study arms

  • Experimental
    Treatment arm

    Metformin orally at doses up to 1500 mg twice daily for 3 months.

    Drug: Metformin

Interventions

  • DrugMetformin

    Metformin orally at doses up to 1500 mg twice daily for 3 months.

06

What researchers measure

Primary outcomes

  1. Overall response

    The primary outcome is the objective response rate (complete responses) after 3 months of treatment with metformin. Evaluable patients are those who have received at least 500 mg metformin twice daily for one week and who undergo a cystoscopy for marker lesion removal.

    Time frame: 3 months

Secondary outcomes

  1. Time to recurrence

    The duration of the time to recurrence of NMIBC after stopping metformin treatment. Patients will be followed for a maximum duration of 5 years.

    Time frame: 5 years

  2. Toxicity of metformin treatment

    The number of grade 1-4 and grade 5 (fatal) NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE) events during treatment with metformin. All patients will be evaluable for toxicity from the time of their first treatment with metformin.

    Time frame: 3 months

  3. Partial response

    At least 30% reduction in the longest diameter of the marker lesion.

    Time frame: 3 months.

07

Study locations

1 of 3 sites recruiting
  • RadboudUMC
    Nijmegen, Gelderland, Netherlands
    Not yet recruiting
  • Sint Franciscus Gasthuis
    Rotterdam, South Holland, Netherlands
    • ER Boeve, MD PhD · Contact
    • ER Boeve, MD PhD · Principal investigator
    Not yet recruiting
  • Academic Medical Center
    Amsterdam, 1105 AZ, Netherlands
    Recruiting
08

References and documents

Publications

  • 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. PubMed 31752752 ↗

Individual participant data

Plan to share: No

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Sep 2019 (actual). Primary completion is estimated for Jul 2024, 58 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 16, 2017
First posted
Dec 20, 2017
StartActual
Sep 1, 2019
Primary completionEst.
Jul 31, 2024
CompletionEst.
Oct 1, 2029
Last update
Sep 21, 2023
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 21, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03379909
Lead sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Radboud University Medical Center
Responsible party
J.W. Wilmink (Medical Oncologist, Associate Professor, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)) — Principal investigator
First posted
Dec 20, 2017
Start date
Sep 1, 2019
Primary completion
Jul 31, 2024 (estimated)
Completion
Oct 1, 2029 (estimated)
Last update
Sep 21, 2023

Study contacts

M. J. Remmelink, MD
Contact
m.j.remmelink@amsterdamumc.nl
0204441376
J. W. Wilmink, MD, PhD
Contact
j.w.wilmink@amsterdamumc.nl
0205665983

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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