Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Immunomodulating Agents

BCG Vaccine

Antimetabolites

Patients will receive Gemcitabine once weekly for 6 weeks.

Gemcitabine will be administered intravesically at a dose of 2000 mg.

Juan Chipollini, MD

Michele Chu-Pilli

UACC IIT

Intravesical immunotherapy or chemotherapy for non-muscle invasive bladder cancer is a well-established treatment for preventing or delaying tumor recurrence after bladder tumor resection. For high-risk non-muscle invasive bladder cancer, immunotherapy in the form of intravesical Bacillus Calmette-Guérin (BCG) can be effective as first-line, nevertheless, the response rate to BCG is suboptimal with many patients failing treatment. Following BCG-failure, however, very few effective therapeutic options exist besides life-changing cystectomy. In addition, nationwide shortages of BCG have pushed the use of alternative intravesical therapies for non-muscle invasive bladder cancer. At Banner University Medical-Tucson, the use of intravesical Gemcitabine is considered as standard treatment for patients with bladder cancer who are unable to get BCG or have failed prior BCG treatment. The role of Gemcitabine as treatment for NBMIC is poorly understood. The purpose of this study is to gain a better understanding of the use of Gemcitabine intravesical chemotherapy for non-muscle invasive bladder cancer in a prospective cohort of patients.

Intravesical Gemcitabine in Patients With NMIBC

Phase II Trial of Intravesical Gemcitabine in Patients With Nonmuscle Invasive Bladder Cancer With or Without Prior Bacillus Calmette-Guérin Therapy

Tissue will be collected for future exploratory analyses. Collected tissue will be stored at the University of Arizona Cancer Center Tissue Acquisition and Cellular/Molecular Analysis Shared Resource (TACMASR) for use in future studies but will not be directly assessed for the purposes of this study.

The primary outcome measure will be CR rate, defined as the percentage of patients with CR at the 3-month visit. An event will be defined as the earliest date of recurrence as determined using the date of cystoscopy, biopsy, or cytology, whichever occurs first.

To assess durable CR in patients who achieved CR at the 3-month visit, defined as the percentage of patients with no detectable disease 6, 9, and 12 months after treatment initiation. Duration of CR will be defined as the time from the date of evidence of CR at the 3-month visit to the earliest date of recurrence.

To assess adverse events using the Medical Dictionary for Regulatory Activities (MedDRA) version 21.0 and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Adverse events will be monitored during the course of treatment, and a toxicity assessment will be done after completion of treatment that will descriptively summarize any treatment-related adverse events that occur on or after the date of the first instillation of gemcitabine.

To assess the number of patients who are agreeable to monthly maintenance therapy for 10 months as per patient and physician discretion.

To assess rate of salvage cystectomy and reasons for cystectomy at the time of tumor recurrence (if any) after treatment with gemcitabine.

University of Arizona

Anti-Infective Agents

Mitomycins

Mitomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

4 once weekly outpatient intravesical instillations 40mg Mitomycin C

Surgical management according to local practice

Patients assigned to the chemoresection group will receive 4 once weekly intravesical instillations of 40mg MMC as outpatients.

Mitomycin C

Patients in this group should be treated according to local practice. Surgical interventions may include transurethral resection (TUR) or ablation.

Surgical Management

Hugh Mostafid

Patients diagnosed with low risk non-muscle invasive bladder cancer (NMIBC) are at risk of frequent low grade recurrence, which usually necessitates surgical intervention under general anaesthetic. This multicentre study aims to establish the short term efficacy of chemoresection using chemotherapy within the bladder for the treatment of NMIBC.

Should the levels of complete response following chemoresection meet predefined criteria, a larger phase III trial would be developed to assess longer term disease related endpoints, with the aim of standardising management of recurrent low risk NMIBC and potentially removing the need for over a thousand patients each year to undergo surgery.

CALIBER is a two stage phase II, multicentre, randomised controlled trial (RCT). A control group has been included to provide prospective data about surgical management and outcomes and assess feasibility of recruitment to a randomised study.

Stage 1: 80 patients will be recruited with treatment allocated 2:1 by randomisation between chemoresection and surgical management.

Stage 2: If the stop/go activity criteria at the end of stage 1 indicate that recruitment should continue, 9 additional participants will be recruited, all of whom will receive chemoresection.

Patients assigned to the chemoresection group will receive 4 once weekly intravesical instillations of 40mg Mitomycin C (MMC) as outpatients. This treatment will be delivered via catheter under local anaesthetic.

Patients assigned to the surgical management group will receive the standard surgical management in use at their hospital for treatment of recurrence which may include a single post-operative installation of 40mg MMC within 24 hours.

All participants will be followed up at 3 weeks from the start of treatment (ie at time of final MMC instillation for chemoresection group) and each will receive a cystoscopy three months from the end of treatment to assess response, in accordance with European Association of Urology (EAU) guidelines.

Subsequent cystoscopic follow up will take place 12 months after treatment if recurrence-free at 3 months and then annually.

Investigating Bladder Chemotherapy Instead of Surgery for Low Risk Bladder Cancer

CALIBER - A Phase II Randomised Feasibility Study of Chemoresection and Surgical Management in Low Risk Non Muscle Invasive Bladder Cancer

Defined as an absence of any tumour following chemoresection and will be assessed visually at 3 month check cystoscopy by patients' urologists. A biopsy of the tumour bed would take place to confirm visual assessment of complete response.

Patients who receive 4 MMC instillations with no more than 14 days between each instillation will be described as fully compliant.

Assessing trans-urethral resection and biopsy rates following initial treatment in both treatment groups

Defined as time from randomisation to the first of muscle invasive bladder recurrence, recurrence in the pelvic nodes, distant metastatic recurrence or death from any cause.

Measuring side effects of both treatments using clinician reported toxicity scales

Assessing side effects and impact of both treatments on patient reported quality of life.

Assessed using prospective data collection of health resource usage.

Time from end of treatment to first relapse, in patients confirmed recurrence free at 3 months

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Intravesical Gemcitabine in Patients With NMIBC	NCT05644041	Urinary Bladder...	Gemcitabine	18 Years -	University of Arizona
Investigating Bladder Chemotherapy Instead of Surgery for Low Risk Bladder Cancer	NCT02070120	Bladder Cancer	Mitomycin C Surgical Manage...	16 Years -	Institute of Cancer Research, United Kingdom

Spots Global Cancer Trial Database for nonmuscle invasive bladder cancer (nmibc)