Photodynamic Trans-urethral Resection of Bladder Tumours (PDD-TURBT) to avoid secondary resections (Re-TURBT) in Non-Muscle Invasive Bladder Cancers (NMIBCs)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universita' Degli Studi Di Roma La Sapienza

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Health Care [N] - Health Care Economics and Organizations [N03]

Trial duration

22 Dec 2025 → ongoing

Decision date (initial)

2024-02-20

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacoeconomic, Therapy, Efficacy

To leverage our expertise in Bladder Cancer (BCa)intraoperative Trans-Uretrhal Resection of Bladder Tumor (TURBT), optical imaging enhancement by photodynamic (PDD)-guided resection, and clinical practice shift to improve the therapeutic algorithm and personalization of Non-muscle Invasive Bladder Cancers (NMIBCs). We aim to provide the highest level of evidence for re-defining European Association of Urology (EAU) Guidelines selecting criteria among NMIBCs who could safely avoid unjustified and unnecessary secondary resection (Re-TURBT) procedures. We intend to demonstrate how our experimental multidisciplinary approach will be not oncological inferior to the current standard of care algorithm thus justifying a paradigmatic shift towards a potentially more sustainable and cost-effective patient-tailored surgical approach in NMIBCs candidate for second look and resection (Re-TURBT). To this purpose, in a homogeneous cohort of pre-operative selected patients, we will determine the proportion of early BCa recurrences (i.e., within 4.5 months follow-up) in those NMIBC treated by standard of care (i.e., TURBT followed by Re-TURBT) compared to our novel algorithm proposal (i.e., primary PDD-TURBT followed by no Re-TURBT).

Secondary objectives 4

1. To determine the proportion of BCa late recurrences (i.e., after 4.5 months follow-up) in patients with NMIBC treated by standard of care compared to our novel algorithm proposal.
2. To determine the proportion of patients that progress from NMIBC to MIBC in patients treated with standard of care compared to our novel algorithm proposal.
3. To determine changes in health-related quality of life (HRQoL) resulting from the physical and psychological benefit along with any harms associated with each strategy and with subsequent additional interventions. We will use generic QoL for cost-effectiveness analysis (i.e., EQ-5D-5L) and specific validated questionnaires to assess the outcomes of interest in the NMIBC population (i.e., EORTC-QLQ-C30 and EORTC QLQ-NMIBC24)
4. To perform a within-trial cost-benefit analysis to calculate incremental cost per Re-TURBT avoided and the cost-utility of the experimental approach as measured by the incremental cost per quality-adjusted life year (QALY) gained at 2 years and over the patients’ lifetime. A sub-analysis regarding specific total hospital costs and social health costs (e.g., productivity cost, informal cost) will be compared between the two arms of treatment.

Conditions and MedDRA coding

Non-muscle invasive bladder cancer (NMIBC)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001245-PIP00-11

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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.
2. Patients with a TUR-confirmed diagnosis of NMIBC and candidate for second look and resection (Re-TURBT) according to EAU Guidelines
3. 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).
4. Patients who never received adjuvant Bacillus of Calmette-Guérin (BCG) immunotherapy (i.e., BCG naïve patients) for previous BCa history
5. Fit to undergo all procedures listed in protocol
6. Able to provide written informed consent

Exclusion criteria 9

1. Contraindication to TURBT and/or Re-TURBT
2. Initial TURBT diagnosis of Muscle-Invasive Bladder Cancer (MIBC, i.e., T2) or locally advanced BCa (i.e., T3-T4).
3. Preoperative evidence of metastatic disease (i.e., cN1 – N3 and/or cM1).
4. Visual evidence of low-risk NMIBC (solitary tumor and/or < 1 cm) before initial TURBT.
5. Visual evidence of MIBC on preliminary cystoscopy (i.e., non-papillary or sessile mass attached directly by its base without a stalk).
6. 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)
7. Concomitant Upper tract (kidney or ureteric) tumours on imaging
8. Contraindication to adjuvant intravesical BCG immunotherapy
9. Unfit to undergo any procedures listed in protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 6

1. 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.
2. 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).
3. The relative proportions of patient with progression to MIBC over follow-up between the experimental and the standard of care arms.
4. 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).
5. 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.
6. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universita' Degli Studi Di Roma La Sapienza

Sponsor organisation

Universita' Degli Studi Di Roma La Sapienza

Address

Viale Regina Elena 324

City

Rome

Postcode

00161

Country

Italy

Scientific contact point

Organisation

Universita' Degli Studi Di Roma La Sapienza

Contact name

Dr Francesco Del Giudice

Public contact point

Organisation

Universita' Degli Studi Di Roma La Sapienza

Contact name

Dr Francesco Del Giudice

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications