The Impact of PDD During TURB for NMIBC (TUR_BLUE)

The Impact of PDD During TURB for NMIBC: a Prospective Randomized Controlled Trial

The goal of this clinical trial is to learn if photodynamic diagnosis (PDD) performed using violet light after intra-vesical instillation of hexaminolaevulinic acid (Hexvix 85mg/50ml) is more sensitive than the standard white light tecnique in detection of malignant bladder tumour.

Patients will be randomised to:

• Transurethral resection of the bladder (TURB) with a standard white light tecnique
• TURB with the PDD tecnique using the study drug Hexvix

Study Overview

• Status: Not yet recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Procedure: Transurethral resection of the bladder performed with PDD tecnique and Hexvix

Detailed Description

Non-muscle invasive pT1 high-grade (HG) bladder cancer (NIMBC) represents a challenge for the urologists due to its aggressive behavior, with a marked tendency to recur after transurethral resection of the bladder (TURB) and even progress to muscle-invasive disease. To limit the risk of upstaging and to provide more clinical information indispensable for the decision-making process, international guidelines strongly recommend a re-TURB to be performed within 2-6 weeks from the first resection in all pT1HG tumors. However, not all the published literature agrees on the value of re-TURB wich is also an invasive and morbid procedure, requires a general or locoregional anesthesia and, like all surgical procedure, it is not free of risks and complications. There is, therefore, an unmet need for improving the quality and completeness of TURB which may have an impact on the necessity of Re-TURB. It has been confirmed that fluorescence-guided biopsy and resection (photodynamic diagnosis-PDD) are more sensitive than conventional procedures for the detection of malignant tumours, particularly for CIS. PDD is performed using violet light after intra-vesical instillation of hexaminolaevulinic acid (Hexvix 85mg/50ml).To date, no randomized controlled trials (RCTs) have been conducted aiming to compare the completeness of TURB with PDD compared to TURB with standard white light (WL).

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Francesco Soria; Phone Number: 0116336594; Email: francesco.soria@unito.it
• Study Contact Backup: Name: Lisa Giacometti; Email: lisa.giacometti@cpo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntarily signed informed consent per Good Clinical Practice and national regulations
• Age ≥ 18 years
• Patient planned for TURB for >1,5 cm suspected (with either abdomen ultrasound or flexible cystoscopy) primary bladder cancer. The cut-off of 1,5cm has been chosen to maximize the probability of enrolling high-risk patients and, consequently, to maximize the probability of performing the re-TURB.

Exclusion Criteria:

• Patients with history of recurrent NMIBC
• Patients with visible incomplete resection during primary TURB
• Patients with metastatic disease or with a preoperative CT scan highly suspected for MIBC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Photodynamic diagnosis using Hexvix; Transurethral resection of the bladder (TURB) is performed using photodynamic diagnosis (PDD) which involves the of use the study drug (Hexvix) to allow for better visualisation and subsequent resection	Procedure: Transurethral resection of the bladder performed with PDD tecnique and Hexvix; For the execution of PDD cystoscopy in blue light, it is necessary to use the study drug (Hexvix) which, after intravesical instillation, causes an accumulation of porphyrins in the lesions of the bladder wall at the intracellular level. The intracellular porphyrins are photoactive fluorescent compounds that emit red light when excited with blue light. Consequently, the preneoplastic and neoplastic lesions will emit a red luminescence against a blue background, allowing for better visualisation and subsequent resection.
No Intervention: White light; Transurethral resection of the bladder (TURB) is performed using the standard white light procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual disease and/or upstaging	Compare the completeness of TURB with PDD vs TURB with WL in terms of proportion of patients with residual disease and/or upstaging at re-TURB	6 to 8 weeks from the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants diagnosed with malignant lesions	Compare the detection of malignant lesions between PDD and WLC using high-definition (HD) equipment during both primary TURB and re-TURB	6 to 8 weeks from the intervention
The European organization for reasearch and treatment of cancer quality of life questionnaire for patients with non-muscle invasive bladder cancern	The scale range from 24 (better outcome) to 96 (worse outcome)	from date of randomization until 20 weeks from randomization
EQ-5D-5L	The scale range from 5 (better outcome) to 25 (worse outcome)	from date of randomization until 20 weeks from randomization
EQ VAS	A self-rating question of overall health status, measured on a 0 (worse outcome) to 100 (better outcome) visual analogue scale	from date of randomization until 20 weeks from randomization
Adverse events	Assess treatment changes and adverse events associated with each technique	from date of randomization until 20 weeks from randomization

Collaborators and Investigators

• Sponsor: A.O.U. Città della Salute e della Scienza
• Collaborators: Photocure
• Investigators: Principal Investigator: Francesco Soria, AOU Città della Salute e della Scienza

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: July 29, 2024
• First Submitted That Met QC Criteria: August 7, 2024
• First Posted (Actual): August 12, 2024

Study Record Updates

• Last Update Posted (Actual): August 12, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: TURB; Hexvix; re-TURB; photodynamic diagnosis-PDD
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: CDS01FS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Participant Data requests should be submitted to the corresponding author for consideration. Access to deidentified participant data may be granted following review, after the publication of major results
• IPD Sharing Time Frame: Data will be available after 6 months from major results publication and for the following 5 years
• IPD Sharing Access Criteria: Data requests should be submitted to the corresponding author for consideration
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No