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

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ClinicalTrials.gov Identifier: NCT03379909
Recruitment Status : Not yet recruiting
First Posted : December 20, 2017
Last Update Posted : March 30, 2018
Sponsor:
Collaborators:
Radboud University
Jeroen Bosch Ziekenhuis
Sint Franciscus Gasthuis
Information provided by (Responsible Party):
J.W. Wilmink, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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 marker tumour deliberately left following transurethral resection of multiple, papillary NMIBC tumours.

Condition or disease Intervention/treatment Phase
Superficial Bladder Cancer Bladder Cancer Drug: Metformin Phase 2

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 marker tumour deliberately left following transurethral resection of multiple, papillary NMIBC tumours. All patients will receive metformin orally at doses up to 1500 mg twice daily. Metformin treatment will start within 2 weeks following transurethral resection, in which all but the marker lesion will be resected. After 3 months of metformin treatment, the effect of metformin on the marker lesion is evaluated by cystoscopy and biopsy under anaesthesia. Residual tumour, if present at this evaluation, will be resected. In case of complete disappearance of the marker lesion the former tumour area will be biopsied.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 49 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Oral Metformin for Intravesical Treatment of Non-muscle-invasive Bladder Cancer
Estimated Study Start Date : October 1, 2018
Estimated Primary Completion Date : January 1, 2021
Estimated Study Completion Date : October 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Experimental: Treatment arm
Metformin orally at doses up to 1500 mg twice daily for 3 months.
Drug: Metformin
Metformin orally at doses up to 1500 mg twice daily for 3 months.




Primary Outcome Measures :
  1. Overall response [ Time Frame: 3 months ]
    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.


Secondary Outcome Measures :
  1. Time to recurrence [ Time Frame: 5 years ]
    The duration of the time to recurrence of NMIBC after stopping metformin treatment. Patients will be followed for a maximum duration of 5 years.

  2. Toxicity [ Time Frame: 3 months ]
    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.

  3. Partial response [ Time Frame: 3 months. ]
    At least 30% reduction in the longest diameter of the marker lesion.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 18 years.
  • Patients with primary or recurrent multiple histologically confirmed Ta or T1 (non-muscle invasive), G1 or G2 (low grade) urothelial carcinoma of the bladder with no evidence of carcinoma in situ.
  • Patients must have at least 2 lesions but no more than 10.
  • The resected lesions must contain detrusor muscle to confirm a Ta/T1 disease.
  • All visible lesions must be completely removed by transurethral resection at entry to the study, except for an untouched marker lesion measuring 0.5-1.0 cm in its greatest dimension.
  • Bimanual examination immediately following transurethral resection under anaesthesia should be carried out and no mass should be felt.
  • Adequate renal function (creatinine <150 μmol/L and/or an eGFR >60 ml/L).
  • 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 having muscle-invasive disease (stage T2 or greater) or CIS.
  • Patients with grade 3 (high-grade) 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03379909


Locations
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Netherlands
RadboudUMC Not yet recruiting
Nijmegen, Gelderland, Netherlands
Contact: JA Witjes, MD PhD         
Principal Investigator: JA Witjes, MD PhD         
Jeroen Bosch Ziekenhuis Not yet recruiting
's-Hertogenbosch, Noord-Brabant, Netherlands
Contact: J Oddens, MD PhD         
Principal Investigator: J Oddens, MD PhD         
Sint Franciscus Gasthuis Not yet recruiting
Rotterdam, Zuid-Holland, Netherlands
Contact: ER Boeve, MD PhD         
Principal Investigator: ER Boeve, MD PhD         
Academic Medical Center
Amsterdam, Netherlands, 1105 AZ
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Radboud University
Jeroen Bosch Ziekenhuis
Sint Franciscus Gasthuis

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Responsible Party: J.W. Wilmink, Medical Oncologist, Associate Professor, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT03379909     History of Changes
Other Study ID Numbers: Medonc-17-11
First Posted: December 20, 2017    Key Record Dates
Last Update Posted: March 30, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by J.W. Wilmink, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
metformin
marker lesion

Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs