Superficial Bladder CancerPhase 2TROJANNCT03379909
Phase II Study of Oral Metformin for Intravesical Treatment of Non-muscle-invasive Bladder Cancer
A Phase 2 study testing Metformin in people with Superficial Bladder Cancer and Bladder Cancer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 3 sites in Netherlands.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Superficial Bladder Cancer, Bladder Cancer
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 3 sitesNetherlands
- Study dates
- 1 Sep 2019to 1 Oct 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands3 sites, 3 recruiting
- Recruiting
Academic Medical Center
Amsterdam, 1105 AZ
J. W. Wilmink, MD, PhD, 31 20 5665955, j.w.wilmink@amsterdamumc.nl
J. R. Oddens, MD, PhD, j.r.oddens@amsterdamumc.nl
- Not yet recruiting
RadboudUMC
Nijmegen, Gelderland
A. G. van der Heijden, MD, PhD, toine.vanderheijden@radboudumc.nl
A. G. van der Heijden, MD PhD
- Not yet recruiting
Sint Franciscus Gasthuis
Rotterdam, South Holland
ER Boeve, MD PhD
ER Boeve, MD PhD
About this study
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.
- Conditions
- Superficial Bladder Cancer, Bladder Cancer
- Being tested
- Metformin
- Keywords
- metformin, marker lesion
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Metformin orally at doses up to 1500 mg twice daily for 3 months.
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Metformin orally at doses up to 1500 mg twice daily for 3 months. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months
Secondary outcomes (3)
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.
Measured: 5 years
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.
Measured: 3 months
Partial response
At least 30% reduction in the longest diameter of the marker lesion.
Measured: 3 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2017
- Study start1 Sep 2019
- Primary completion31 Jul 2024 (estimated)
- Study completion1 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Superficial Bladder CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center
- Responsible party
- Principal investigator, J.W. Wilmink, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03379909
- Sponsor's protocol ID
- Medonc-17-11
- Acronym
- TROJAN
- Status last verified
- Sep 2023
- First submitted
- 16 Dec 2017
- Last updated
- 21 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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