HEXAMINOLEVULINATE for Non-muscle invasive bladder cancer

Inclusion criteria

• {"criterion_text":"- Female and Male patients at least 18 years old referred for clinical suspicion of primary or recurrent BCa who have been advised to undergo TURBT.\n- Patients with a TUR-confirmed diagnosis of NMIBC and candidate for second look and resection (Re-TURBT) according to EAU Guidelines\n- No imaging evidence (i.e., mpMRI/VI-RADS score 1 or 2) of muscle-invasive, locally advanced, or metastatic BCa (i.e., only confirmed CIS, Ta, T1, N0, M0 will be considered eligible).\n- Patients who never received adjuvant Bacillus of Calmette-Guérin (BCG) immunotherapy (i.e., BCG naïve patients) for previous BCa history\n- Fit to undergo all procedures listed in protocol\n- Able to provide written informed consent"}

Exclusion criteria

• {"criterion_text":"- Contraindication to TURBT and/or Re-TURBT\n- Initial TURBT diagnosis of Muscle-Invasive Bladder Cancer (MIBC, i.e., T2) or locally advanced BCa (i.e., T3-T4).\n- Preoperative evidence of metastatic disease (i.e., cN1 – N3 and/or cM1).\n- Visual evidence of low-risk NMIBC (solitary tumor and/or < 1 cm) before initial TURBT.\n- Visual evidence of MIBC on preliminary cystoscopy (i.e., non-papillary or sessile mass attached directly by its base without a stalk).\n- TURBT diagnosis of NMIBCs not eligible for Re-TURBT according to EAU Guidelines (i.e., Ta-LG; Ta-HG with detrusor muscle in the specimen; primary CIS)\n- Concomitant Upper tract (kidney or ureteric) tumours on imaging\n- Contraindication to adjuvant intravesical BCG immunotherapy\n- Unfit to undergo any procedures listed in protocol"}

Primary endpoints

• {"endpoint_text":"- The relative proportions of patients with early BCa recurrence detected during first follow-up cystoscopy will be compared between the experimental and the standard of care arms. Given the different timetable pathway of the two arms under investigation, early BCa recurrence is defined in the experimental arm as any BCa recurrence at 3-months from primary PDD-TURBT while at 3-months from WL Re-TURBT in the standard of care arm.","definition_or_measurement_approach":"Early BCa recurrence defined as any bladder cancer recurrence at 3 months post-primary PDD-TURBT in experimental arm and at 3 months post-WL Re-TURBT in standard of care arm; measured by first follow-up cystoscopy and comparison of proportions between arms."}

Secondary endpoints

• {"endpoint_text":"- The relative proportions of patient with late BCa recurrences (i.e., detected after 4.5 months follow-up) between the experimental and the standard of care arms.\n- Time to late BCa recurrences (i.e., late disease-free interval), defined as first recurrence (including progression to muscle-invasive disease, distant metastases, and death due to bladder cancer) in patients without an early recurrence who had follow-up after 4.5 months (landmark analysis). Patients still alive without recurrence will be censored at the last follow-up. The time will be censored at death and/or radical cystectomy in the absence of recurrence (competing risk).\n- The relative proportions of patient with progression to MIBC over follow-up between the experimental and the standard of care arms.\n- Time to progression to MIBC (i.e., progression-free interval) defined as the time from randomization to first increase to BCa stage T2 or higher or distant metastases. Patients still alive without progression will be censored at the last follow-up. The time will be censored upon death and/or radical cystectomy before progression (competing risks).\n- Standardized mean difference of total in-hospital cost and informal costs between the experimental and the standard of care arms. We will model costs and health state changes over a patient lifetime to estimate the incremental cost per Re-TURBT avoided, QALYs and costs to the NHS. This will be based on the updated version of the existing National Institute of Health Research (NIHR) HTA economic model using 2-year data from within the trial.\n- Health related quality of life (HRQoL) from the administered questionnaires will be compared at three years between the experimental and the standard of care arms. Subsequently, these outcomes will be modelled over a patient lifetime time horizon using trial data.","definition_or_measurement_approach":"Late recurrences: detected after 4.5 months. Time-to-event endpoints use censoring rules as specified (censor at last follow-up, death, or radical cystectomy as competing risks). Costs: within-trial and modelled over lifetime using NIHR HTA economic model with 2-year trial data. HRQoL measured by EQ-5D-5L, EORTC-QLQ-C30 and EORTC QLQ-NMIBC24 and compared at 3 years and modelled thereafter."}

Italy

Earliest CTIS Part Ii Submission Date

27-01-2024

Latest Decision Or Authorization Date

20-02-2024

Processing Time Days

24

Number Of Sites

1

Number Of Participants

258

Primary sponsor

Full Name

Universita' Degli Studi Di Roma La Sapienza

Organisation Type

Educational Institution

Country Of Registered Address

Italy