Bladder CancerEarly Phase 1RESECTNCT03266900
A Superiority Trial to Compare Re-resection of High-grade T1 Bladder Urothelial Carcinoma to no Re-resection for Improving Progression Free Survival
A Early Phase 1 study testing re-TURBT and 6 weeks BCG instillation in people with Bladder Cancer and Bladder Urothelial Carcinoma, run by University Health Network, Toronto at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Bladder Cancer, Bladder Urothelial Carcinoma
- What is being tested?
- re-TURBT and 6 weeks BCG instillation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteCanada
- Study dates
- 16 Nov 2017to 4 Oct 2021
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
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.
Read the 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.
- Conditions
- Bladder Cancer, Bladder Urothelial Carcinoma
- Being tested
- re-TURBT, 6 weeks BCG instillation
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
re-TURBTProcedure or surgery
2nd bladder biopsy within 4-6 weeks of initial biopsy
6 weeks BCG instillationDrug
standard 6 weeks of BCG induction
| Study group | Role | What they receive |
|---|---|---|
| re-TURBT | Experimental | Patients in this arm will receive a 2nd TURBT within 4-6 weeks of initial TURBT Receives: Procedure: re-TURBT |
| 6 BCG instillations | Active comparator | Patients in this arm will not receive a 2nd TURBT, but will receive 6 instillations of BCG. Receives: Drug: 6 weeks BCG instillation |
What is being measured
The primary outcome is the main question the study is designed to answer.
5 year Progression Free Survival
Measured: 5 years
Secondary outcomes (4)
Clinical Measures - These include recurrence free survival (in the bladder), time to cystectomy, and metastases-free survival as measured over time from intervention to 5-years post-intervention.
- Time to bladder recurrence (ie. BCG failure), measured over time from intervention to 5-years post-intervention.
- Time to cystectomy, measured over time from intervention to 5-years post-intervention.
- Time to metastasis (lymph node or distant metastasis), measured over time from intervention to 5-years post-intervention.
Measured: 5 years
Survival Measures - These include disease specific survival and overall survival as measured over time from intervention to 5-years post-intervention.
- Time to bladder cancer-specific mortality, measured over time from intervention to 5-years post-intervention
- Time to death (examining overall survival), measured over time from intervention to 5-years post-intervention.
Measured: 5 years
Perioperative Safety Measures - These include rate of major complications as defined by the Clavien-Dindo classification as grade 3, 4, and 5.
Proportion with major complications, indicated by the Clavien-Dindo classification of grade 3, 4, and 5, measured during the repeat TURBT hospitalization period.
Measured: 5 years
Mean Change of Patient FACT BI Scores - This includes prospective collection with a validated BCa HRQOL instruments performed at each patient visit.
- 1-year post-intervention from baseline
- Over time at each 3-month surveillance visit (during the first 2 years), each 6-month surveillance visit (during the year 2-3), and each annual surveillance visit (during year 4-5).
The FACT-Bl metric is validated for measuring HRQOL of patients with BCa. This questionnaire is designed for patients with bladder cancer and includes assessment of four general domains (physical, social/family, emotional and function), with patients responding to statements on a five-point ordinal Likert scale ranging from zero to four. Additionally, there are statements concerning urinary tract symptoms, intestinal symptoms and sexual symptoms (10 statements), with two more for those with a stoma. With 39 statements, the highest score achievable is 156.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2017
- Study start16 Nov 2017
- Primary completion4 Oct 2021
- Study completion4 Oct 2021
Why it stopped: Difficulties with accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Bladder Cancer Canada, Canadian Urological Association, Canadian Urologic Oncology Group
- Responsible party
- Sponsor
- Investigators
- Girish Kulkarni, MD PhD FRCSC, Principal investigator, University Health Network - Princess Margaret Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03266900
- Sponsor's protocol ID
- 17-5305.0
- Acronym
- RESECT
- Status last verified
- Apr 2022
- First submitted
- 9 Aug 2017
- Last updated
- 20 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03266900
- Acronym / sponsor ID
- RESECT / 17-5305.0
- Conditions
- Bladder Cancer, Bladder Urothelial Carcinoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulties with accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Bladder Cancer Canada, Canadian Urological Association, Canadian Urologic Oncology Group
- Study start
- 16 Nov 2017 (actual)
- Primary completion
- 4 Oct 2021 (actual)
- Study completion
- 4 Oct 2021 (actual)
- First posted
- 30 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| re-TURBT | Experimental | Procedure: re-TURBTPatients in this arm will receive a 2nd TURBT within 4-6 weeks of initial TURBT |
| 6 BCG instillations | Active comparator | Drug: 6 weeks BCG instillationPatients in this arm will not receive a 2nd TURBT, but will receive 6 instillations of BCG. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| re-TURBT2nd bladder biopsy within 4-6 weeks of initial biopsy | Procedure or surgery | re-TURBT |
| 6 weeks BCG instillationstandard 6 weeks of BCG induction | Drug | 6 BCG instillations |
Primary outcome
5 year Progression Free Survival
Time frame: 5 years
4 secondary outcomes
Clinical Measures - These include recurrence free survival (in the bladder), time to cystectomy, and metastases-free survival as measured over time from intervention to 5-years post-intervention.
Time frame: 5 years
Survival Measures - These include disease specific survival and overall survival as measured over time from intervention to 5-years post-intervention.
Time frame: 5 years
Perioperative Safety Measures - These include rate of major complications as defined by the Clavien-Dindo classification as grade 3, 4, and 5.
Time frame: 5 years
Mean Change of Patient FACT BI Scores - This includes prospective collection with a validated BCa HRQOL instruments performed at each patient visit.
Time frame: 5 years
Results and safety
The study was stopped early (reason given: Difficulties with accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Girish Kulkarni, MD PhD FRCSC principal investigator
University Health Network - Princess Margaret Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing re-TURBT and 6 weeks BCG instillation in people with Bladder Cancer and Bladder Urothelial Carcinoma, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulties with accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
5 year Progression Free Survival (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2022.