NCT03379909

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
49

participants targeted

Target at P25-P50 for phase_2

Timeline
42mo left

Started Sep 2019

Longer than P75 for phase_2

Geographic Reach
1 country

3 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress66%
Sep 2019Oct 2029

First Submitted

Initial submission to the registry

December 16, 2017

Completed
4 days until next milestone

First Posted

Study publicly available on registry

December 20, 2017

Completed
1.7 years until next milestone

Study Start

First participant enrolled

September 1, 2019

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2024

Completed
5.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2029

Expected
Last Updated

September 21, 2023

Status Verified

September 1, 2023

Enrollment Period

4.9 years

First QC Date

December 16, 2017

Last Update Submit

September 19, 2023

Conditions

Keywords

metforminmarker lesion

Outcome Measures

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.

    3 months

Secondary Outcomes (3)

  • Time to recurrence

    5 years

  • Toxicity of metformin treatment

    3 months

  • Partial response

    3 months.

Study Arms (1)

Treatment arm

EXPERIMENTAL

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

Drug: Metformin

Interventions

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

Treatment arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

RadboudUMC

Nijmegen, Gelderland, Netherlands

NOT YET RECRUITING

Sint Franciscus Gasthuis

Rotterdam, South Holland, Netherlands

NOT YET RECRUITING

Academic Medical Center

Amsterdam, 1105 AZ, Netherlands

RECRUITING

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Non-Muscle Invasive Bladder NeoplasmsUrinary Bladder Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary Bladder DiseasesUrologic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic Chemicals

Central Study Contacts

M. J. Remmelink, MD

CONTACT

J. W. Wilmink, MD, PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Medical Oncologist, Associate Professor

Study Record Dates

First Submitted

December 16, 2017

First Posted

December 20, 2017

Study Start

September 1, 2019

Primary Completion

July 31, 2024

Study Completion (Estimated)

October 1, 2029

Last Updated

September 21, 2023

Record last verified: 2023-09

Data Sharing

IPD Sharing
Will not share

Locations