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BRIEF TITLE: A Pilot, Single-centre, Randomized, 5-year, Parallel-group, Superiority Trial to Compare Re-resection of High-grade T1 Bladder Urothelial Carcinoma to no Re-resection for Improving Progression Free Survival

A Pilot, Single-centre, Randomized, 5-year, Parallel-group, Superiority Trial to Compare Re-resection of High-grade T1 Bladder Urothelial Carcinoma to no Re-resection for Improving Progression Free Survival


  • Org Study ID: 17-5305.0
  • Secondary ID:
  • NCT ID: NCT03266900
  • NCT Alias:
  • Sponsor: University Health Network, Toronto - Other
  • Source: University Health Network, Toronto

Brief Summary

The investigators would like to compare the progression free survival, overall survival, quality of life, and safety outcomes of patients receiving versus not receiving a 2nd transurethral resection of bladder tumor.

Detailed Description


Background: Bladder cancer (BCa) is the 4th and 12th most common malignancies by incidence in
Canadian men and women, respectively. In Canada, the lifetime probability of developing BCa
is 1 in 27 men and 1 in 84 women. Urologists use a transurethral resection of bladder tumor
(TURBT) to diagnose and stage patients with non-muscle invasive bladder cancer (NMIBC). While
the value of repeat TURBT is not questioned for incomplete endoscopic resections,
retrospective studies have suggested value in repeat resection for high grade T1 (T1HG)
tumors even if they are completely resected, typically done within 6 weeks of the initial
resection. Repeat TURBT for T1HG BCa has been touted to detect understaged tumors, remove
occult residual disease, provide prognostic value and improve subsequent bladder therapy. To
date, there is a paucity of high quality level-1 evidence validating repeat TURBT for T1HG
compared to a single TURBT for improved long term disease specific outcomes.

Research Question: Among patients with T1HG BCa with completely resected tumor, is repeat
TURBT superior to single TURBT for improving 53-year progression free survival (PFS), defined
as >/=T2 local disease or lymph node disease/distant metastasis? Study Design: The RESECT
trial is designed as a pilot, single-centre, 2-arm parallel-group, superiority randomized
trial, with random permuted blocks (lengths of 4 or 6) and balanced allocation (1:1),
conducted at the University Health Network.

Patient Population: Adult patients with completely resected T1HG bladder urothelial carcinoma
are eligible to participate. Patients with either lymph node/distant metastases at
presentation, variant histology, those that had their initial resection performed outside of
a study centre, or patients with severe comorbidities are excluded.

Intervention: Repeat TURBT (experimental) versus T1HG standard of care (active control).

Outcomes: The primary outcome is the difference between the two intervention arms with
regards to PFS over 5-years of follow-up. Secondary outcomes are the difference between the
two intervention arms in: (i) clinical measures; (ii) survival measures; (iii) perioperative
safety measures; and (iv) quality of life (QOL) questionnaires.

Randomization: Randomization will occur at the central coordinating site using a
computer-generated randomization schedule and random permuted blocks (of lengths 4 or 6). The
allocation sequence will be implemented using sequentially numbered, opaque, sealed
envelopes.

Blinding: Neither participants nor treating physicians will be blinded to treatment
allocation. The research/data analyst team will be blinded as will the radiologists that
assess surveillance imaging.

Sample Size: To test feasibility, a sample of 18 cases in 1 year is expected. Analysis:
Proportional outcomes will be analyzed with Chi-square or Fisher's exact test and continuous
variables will be analyzed with Student's t-test. Time to event outcomes will be analyzed
using log-rank tests on Kaplan-Meier estimates, followed by adjusted Cox proportional-hazard
models. Continuous variables with differences between two time periods will be analyzed suing
an analysis of covariance, with baseline values and centre adjusted for as covariates.
Continuous variable outcomes with values over multiple time periods will be analyzed using
repeated measures analysis of covariance.

Follow-Up: In addition to baseline assessment, each participant will be followed up at 3, 6,
9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months after the intervention with cystoscopic
evaluation, and assessment of disease progression and QOL. Surveillance imaging will be every
6 months for the 5-year follow-up.

Overal Status Start Date Phase Study Type
Recruiting November 16, 2017 Early Phase 1 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: 5 year Progression Free Survival

Primary Outcome 1 - Time Frame: 5 years

Condition:

  • Bladder Cancer
  • Bladder Urothelial Carcinoma

Eligibility

Criteria:
Inclusion Criteria:

- Complete initial resection by a BCa-focused urologic oncologist; mandatory bladder
detrusor muscle in the initial TURBT specimen and complete visible resection
documented by the surgeon/OR staff by intra-operative photography.

- Urothelial carcinoma as the predominant histology as determined by genitourinary
specific pathologist (e.g. small (<50%) components of small cell, squamous cell or
adenocarcinoma are allowable).

- Able and willing to consent.

- ≥18 years old: BCa is primarily a disease of the elderly, thus we have elected to
include healthy octogenarian/nonagenarian patients. Additionally, since a TURBT can be
performed under general or spinal anesthesia, we feel that including these patients is
acceptable.

Exclusion Criteria:

- Lymph node or distant metastases at initial presentation - determined on standard BCa
staging evaluation with a CT-urogram of the abdomen/pelvis and/or a preoperative chest
x-ray demonstrating pulmonary metastases.

- Extensive NMIBC disease warranting immediate cystectomy.

- Variant histology (not urothelial carcinoma) - ie. micropapillary, plasmacytoid,
nested or sarcomatoid variants.

- No muscularis propria (inadequate bladder staging) present in the initial TURBT
specimen.

- Initial TURBT demonstrating T1HG disease performed outside of study centre - as per
study protocol, quality control of surgical performance for this trial requires the
TURBT to be performed by an experienced BCa-dedicated surgeon.

- Patients with severe comorbidities, including but not limited to: (i) previous stroke
with persistent cognitive, motor, etc deficits; (ii) recent (<6 months) myocardial
infarction or current unstable angina; (iii) liver cirrhosis; (iv) severe chronic
obstructive pulmonary disease (COPD)/respiratory disease. Patients must be suitable
candidates for either spinal or general anesthesia.

- Pregnancy or lactation.
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Gender: All

Minimum Age: 18 Years

Maximum Age: 100 Years

Healthy Volunteers: No

Official Information

Name: Girish Kulkarni, MD PhD FRCSC

Role: Principal Investigator

Affiliation: University Health Network - Princess Margaret Hospital

Overall Contact

Name: Kathy Li, MPH

Phone: 4169464501

Email: kathy.li@uhn.ca

Location

Facility Status Contact
University Health Network
Toronto, Ontario M5G2M9
Canada
Recruiting