Active Surveillance vs Treatment for Bladder Cancer

(NEO-BLAST Trial)

Overseen By Marie-Pier St-Laurent, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Peter Black

Must be taking: Cisplatin-based chemotherapy

Must not be taking: Immunotherapy, Antibody-drug conjugates

Disqualifiers: Small cell histology, Prior chemotherapy, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

688 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have received any systemic therapy for urothelial carcinoma or certain other treatments within 2 years, you may not be eligible to participate.

What data supports the effectiveness of the treatment Active Surveillance, Watchful Waiting, Observation, Definitive bladder treatment for bladder cancer?

The research suggests that different surveillance strategies, like low- versus high-intensity cystoscopic surveillance, can impact outcomes for bladder cancer patients, indicating that careful monitoring may be beneficial. However, there is no direct evidence from the provided studies specifically supporting the effectiveness of active surveillance as a treatment for bladder cancer. ^{1 2 3 4 5}

Is active surveillance safe for bladder cancer patients?

Research on active surveillance for low-grade bladder tumors suggests it is generally safe for patients, as it involves monitoring without immediate surgery. ^{1 2 6 7 8}

How does definitive bladder treatment differ from other treatments for bladder cancer?

Definitive bladder treatment often involves a combination of chemotherapy and radiotherapy, which is shown to be more effective than radiotherapy alone for invasive bladder cancer. This approach aims to preserve the bladder while requiring ongoing surveillance to manage the risk of new or recurring cancer. ^{9 10 11 12 13}

Research Team

Peter Black, MD

Principal Investigator

University of British Columbia

Eligibility Criteria

This trial is for individuals with invasive bladder cancer who have completed initial systemic treatment. It aims to identify those without remaining cancer using advanced imaging, biopsies, and tumor DNA detection in blood/urine. Participants must be eligible for randomization to active surveillance or conventional treatment.

Inclusion Criteria

I am over 18 years old.

Participants must be able to undergo pelvis MRI

My bladder cancer has grown into the muscle layer.

Exclusion Criteria

Pregnancy

I haven't had chemotherapy or immunotherapy in the last 2 years.

My cancer does not have small cell or plasmacytoid features.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Therapy

Participants receive standard of care neoadjuvant therapy (NAT) for muscle-invasive bladder cancer

8-12 weeks

Regular visits for treatment administration and monitoring

Clinical Restaging

Participants undergo clinical restaging to assess complete clinical response (cCR) using ctDNA, MRI, and bladder biopsies

4 weeks

1 visit for imaging and biopsies

Randomization and Treatment

Participants with cCR are randomized to active surveillance or definitive bladder treatment (radical cystectomy or chemo-radiation)

Varies based on treatment arm

Follow-up

Participants are monitored for safety and effectiveness after treatment with regular cystoscopy, cytology, and imaging

24 months

Cystoscopy every 3 months for 2 years; imaging at 3, 6, 12, 18, and 24 months

Treatment Details

Interventions

• Active Surveillance
• Definitive bladder treatment

Trial Overview The NEO-BLAST study tests whether patients with no evidence of bladder cancer after chemotherapy can safely undergo active surveillance instead of immediate definitive bladder treatment (removal or chemo-radiation). This pilot RCT will use MRI, biopsies, and biomarkers for decision-making.

Participant Groups

Group I: cCR, Active surveillance Experimental Treatment 1 Intervention

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)

Group II: non-cCR, standard of care Active Control 1 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.

Group III: cCR, Standard of care Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Peter Black

Lead Sponsor

Trials

1

Recruited

690+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

Bacillus Calmette-Guérin (BCG) therapy significantly reduces the risk of bladder cancer recurrence and progression compared to transurethral bladder tumor resection alone, based on a systematic review of 39 trials.

While BCG is effective, it is associated with higher rates of local and systemic adverse events compared to other intravesical therapies, highlighting the need to weigh its benefits against potential harms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical Therapy for the Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis. Chou, R., Selph, S., Buckley, DI., et al.[2022]

An active surveillance program for patients with recurrent small bladder cancer (less than 10 mm) showed minimal risk, allowing for monitoring without immediate tumor resection, with 31 patients participating over a mean period of 16.1 months.

Out of 43 surveillance periods, most were terminated due to tumor growth or new tumors, but all resected tumors remained at stage Ta, indicating that this approach can be safe and effective for managing low-grade bladder tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active surveillance of low grade bladder tumors. Gofrit, ON., Shapiro, A.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Upper tract surveillance in primary bladder cancer follow-up. [2006]

2. United States pubmed.ncbi.nlm.nih.gov

The impact of low- versus high-intensity surveillance cystoscopy on surgical care and cancer outcomes in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). [2021]

3. China pubmed.ncbi.nlm.nih.gov

[Effects of neoadjuvant chemotherapy on the prognostic mortality risk of invasive transitional bladder cancer: a meta-analysis]. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Survival of patients with bladder cancer from a UK hospital: a 10-year follow-up study. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Pathologic response in patients receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer: Is therapeutic effect owing to chemotherapy or TURBT? [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Disease specific mortality in patients with low risk bladder cancer and the impact of cystoscopic surveillance. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Intravesical Therapy for the Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Active surveillance of low grade bladder tumors. [2016]

9. United States pubmed.ncbi.nlm.nih.gov

Combined chemotherapy and external beam radiotherapy for transitional cell carcinoma of the bladder. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Adjuvant chemotherapy for bladder cancer-why does level 1 evidence not support it? [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

When and How To Perform Active Surveillance for Low-risk Non-muscle-invasive Bladder Cancer. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Surveillance guidelines based on recurrence patterns after radical cystectomy for bladder cancer: the Canadian Bladder Cancer Network experience. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Commentary on "Surveillance guidelines based on recurrence patterns after radical cystectomy for bladder cancer: the Canadian Bladder Cancer Network experience." Yafi FA, Aprikian AG, Fradet Y, Chin JL, Izawa J, Rendon R, Estey E, Fairey A, Cagiannos I, Lacombe L, Lattouf JB, Bell D, Saad F, Drachenberg D, Kassouf W. Department of Surgery (Urology), McGill University, Quebec, Canada: BJU Int 2012;110(9):1317-23 [Epub 2012 Apr 13]. [2018]