NEO-BLAST: Neoadjuvant Therapy for Bladder Cancer Followed by Active Surveillance vs Treatment

NCT06537154 | Recruiting Phase 2 DMC

• 1 other identifier: H23-02447
• Study Type: interventional
• Target: 688
• Locations: 1 country
• Sites: 1

Brief Summary

Invasive bladder cancer is managed with neoadjuvant therapy followed by bladder removal (cystectomy). Research shows that approximately 40% of patient will have no remaining cancer left in their bladder after completion of the initial systemic treatment, and perhaps could have avoided the surgery. However, currently physicians lack the ability to identify these patients. The investigators believe that by using advanced imaging (MRI), bladder biopsies and novel biomarkers that detect tumor DNA in blood, they can better identify participants without any remaining cancer after chemotherapy. This will make active surveillance of these participants safer. In this study, participants without evidence of residual cancer will be randomized to active surveillance vs conventional bladder treatment (bladder removal, or chemo-radiation of the bladder). This study will be a pilot randomized control trial (RCT), and if successful, it will transition to a larger phase 3 RCT.

Conditions

Muscle-Invasive Bladder Carcinoma

Keywords

Muscle invasive bladder urothelial carcinoma; Bladder Cancer

Outcome Measures

Primary Outcomes (2)

• Proportion of patients found to have a cCR and randomized on the number of patients enrolled (pilot-RCT ; phase 2)

  Feasibility to randomized patients with cCR to either active surveillance or definitive bladder treatment.

  24 months

• Metastasis free survival at 2 years (phase 3)

  Time to metastasis, defined as \>cN1 (more than 1 clinically suspicious lymph nodes), cT4a (unresectable disease), or M1 disease or death.

  24 months

Secondary Outcomes (6)

• Bladder-intact event-free survival

  24 months

• Proportion of cCR patient with ypT0

  24 months

• Overall survival

  24 months

• Acceptance rate to treatment allocation

  6 months

• Quality of life measure by EORTC-QLQ-C30 in participants according to treatment received

  24 months

Study Arms (3)

cCR, Standard of care

ACTIVE COMPARATOR

Participants found to have a clinical complete response following NAT randomized to standard of care, described as "definitive bladder treatment", which consists of either radical cystectomy, or chemo-radiation of the bladder

Procedure: Control arm - Definitive bladder treatment

cCR, Active surveillance

EXPERIMENTAL

Participants found to have a clinical complete response following NAT randomized to the investigational arm consisting of active surveillance. They will have have no local treatment to their bladder and will be monitored with cystoscopy, cytology and imaging (active surveillance)

Procedure: Active Surveillance

non-cCR, standard of care

NO INTERVENTION

Participants found to have residual urothelial carcinoma (not cCR) will received the standard of care definitive bladder treatment. They will received either radical cystectomy or chemo-radiation of the bladder.

Interventions

Active Surveillance PROCEDURE

Participant found to have a cCR will be randomized to either standard of care or investigational active surveillance.

Also known as: Clinical restaging (utDNA, ctDNA, MRI and TURBT)

cCR, Active surveillance

Control arm - Definitive bladder treatment PROCEDURE

Standard of care, consisting of radical cystectomy or chemo-radiation of the bladder

cCR, Standard of care

Eligibility Criteria

• Age: 19 Years+
• Gender Eligibility Details: All genders are eligible
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female \>18 years
• Primary urothelial or predominantly (\>50%) urothelial carcinoma of the bladder with histologic evidence of muscularis propria invasion.
• Clinical stage T2-T4aN0M0 (Radiographic lymphadenopathy greater than 1.5 cm in short axis by imaging must be proven by biopsy to be free of cancer)
• No concomitant multifocal carcinoma in situ; a single focus is allowed.
• ECOG performance status 0, 1, or 2.
• Participants must be able to undergo pelvis MRI.
• Medically appropriate candidate for radical cystectomy (assessed by uro-oncologist) or chemo-radiation (assess by radiation-oncologist and medical-oncologist)
• Participants must be candidate to received standard of care (SOC) neoadjuvant systemic treatment at time of enrolment (assessed by medical-oncologist): 4 or more cycles of cisplatin-based chemotherapy (gemcitabine/cisplatin (GC) or methotrexate/vinblastine/Adriamycin/cisplatin (MVAC) or dose-dense MVAC (ddMVAC). If SOC evolves from the time of trial design and enrolment, eligibility to any SOC NAT (for example immunotherapy and/or antibody drug conjugate, as per NCCN guideline) will be allowed.
• Adequate bladder function and/or absence of significant urethral stricture to allow cystoscopic surveillance, as evaluate by urologist.

You may not qualify if:

• Any component of small cell or plasmacytoid histology.
• Prior systemic chemotherapy or immunotherapy (an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) or antibody-drug conjugate (NECTIN-4, HER2 or other) : Participants who have received any previous systemic therapy for urothelial carcinoma or cytotoxic chemotherapy, immunotherapy or other targeted therapy for another malignancy within 2 year of study entry are ineligible.
• No available bladder tumor tissue from prior TURBT for tumor sequencing.
• Prior or concurrent malignancy of any other site EXCEPT for non-melanoma skin cancer OR low risk malignancy not requiring treatment (such as prostate cancer Grade Group 1 under adequate surveillance, carcinoma in situ of the breast, cervix, etc.) AND unless free of disease for ≥ 5 years. Other cancers at low risk of recurrence may be allowed after review by principal investigator.
• Prior radiation therapy for bladder cancer.
• Participants who have received experimental agents within 4 weeks of study entry.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined by current oral or intravenous antibiotic therapy), symptomatic congestive heart failure (NYHA \>2), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnancy. People of childbearing potential must have a negative serum pregnancy test before general anesthesia procedure and MRI
• No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed.

Sponsors & Collaborators

• Peter Black: lead
• University of British Columbia: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Vancouver Prostate Centre

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Watchful Waiting; Circulating Tumor DNA; Magnetic Resonance Spectroscopy; Transurethral Resection of Bladder

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Cell-Free Nucleic Acids; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides; DNA, Neoplasm; DNA; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Peter Black, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie-Pier St-Laurent, MD

CONTACT

604-875-5003; mst-laurent@prostatecentre.com

Jacquie Stevenson

CONTACT

604-875-5003; jstevenson@prostatecentre.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 29, 2024
• First Posted: August 5, 2024
• Study Start: July 28, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)