Bladder Preservation for Muscle Invasive Bladder Cancer

Overseen By Clinical Trial Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Leslie Ballas

Disqualifiers: Diffuse cis, Bilateral hydronephrosis, Prior pelvic radiotherapy, 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: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating muscle invasive bladder cancer with an unusual cell type. Researchers are evaluating the effectiveness of administering chemotherapy, possibly with immunotherapy (which helps the immune system fight cancer), before combining surgery, chemotherapy, and radiation, known as Trimodal Therapy (TMT). The goal is to determine if this method can be implemented quickly enough to prevent cancer from spreading. This trial targets individuals with muscle invasive bladder cancer who have a specific type of cancer cell and have not received previous pelvic radiation or other cancer treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

In earlier studies, trimodal therapy (TMT) for bladder cancer has shown promising results. Research indicates that TMT works about as well as major surgery, without causing more harmful side effects than expected.

Another study found that only 1-2% of patients needed bladder removal due to TMT's side effects. This suggests most patients tolerate TMT well and can keep their bladders.

Overall, these findings suggest TMT is generally safe and well-tolerated for treating muscle-invasive bladder cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Trimodal Therapy (TMT) is unique because it offers a bladder-preserving alternative for muscle invasive bladder cancer, which traditionally involves radical cystectomy, the surgical removal of the bladder. TMT combines three treatments: neoadjuvant chemotherapy, transurethral resection of bladder tumor (TURBT), and concurrent chemotherapy with radiation. This approach not only aims to eliminate the cancer but also preserves the bladder, potentially improving quality of life for patients. Researchers are excited about TMT because it could provide an effective treatment option with fewer life-altering consequences compared to bladder removal.

What evidence suggests that this trial's treatments could be effective for muscle invasive bladder cancer?

Research has shown that trimodal therapy (TMT), which includes surgery, chemotherapy, and radiation, can effectively treat muscle invasive bladder cancer (MIBC). One study found that patients who received TMT had a 5-year survival rate of 30%. Although this is lower than the 48% survival rate for those who underwent bladder removal (a procedure called radical cystectomy, or RC), TMT remains a valuable option, especially for those wishing to preserve their bladder. TMT might also lead to a better quality of life compared to RC. However, it is important to note that TMT may incur higher costs over time due to increased treatment expenses. ^{3 6 7 8 9}

Who Is on the Research Team?

Leslie Ballas

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with a specific type of bladder cancer called Muscle Invasive Bladder Cancer (MIBC) that has unusual cell types (variant histology). Participants must have completed at least 3 cycles of chemotherapy, with or without immunotherapy, and be ready to undergo trimodal therapy combining chemo and radiation.

Inclusion Criteria

Written informed consent obtained from subject and ability for subject to comply with the requirements of the study

My bladder cancer is invasive but hasn't spread beyond the bladder.

Exclusion Criteria

I do not have swelling in both kidneys due to urine buildup.

My pathology report shows widespread abnormal cells.

I have had radiation treatment to my pelvic area.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive at least 3 cycles of neoadjuvant chemotherapy with or without immunotherapy

9-12 weeks

Trimodal Therapy

Participants undergo trimodal therapy consisting of TURBT followed by concurrent chemotherapy with radiation therapy

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Trimodal Therapy (TMT)

Trial Overview The study is testing if a combination treatment approach for MIBC with variant histology—chemo followed by chemoradiation—is effective when started within 45 days after initial chemo. It compares these patients' outcomes to past patients who had standard bladder cancer treated similarly.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 1 Intervention

Neoadjuvant chemotherapy followed by trimodal therapy consisting of TURBT followed by concurrent chemotherapy with radiation therapy

Who Is Running the Clinical Trial?

Leslie Ballas

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

Bladder-preserving trimodal therapy (TMT) and radical cystectomy (RC) showed no significant difference in overall survival and progression-free survival for patients with muscle-invasive bladder cancer, based on a review of 11 studies involving a total of 2682 records.

However, cancer-specific survival was better for patients who underwent radical cystectomy, suggesting that while TMT may be a viable option, RC may offer better outcomes in terms of cancer-specific survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Muscle-invasive bladder cancer organ-preserving therapy: systematic review and meta-analysis. García-Perdomo, HA., Montes-Cardona, CE., Guacheta, M., et al.[2019]

Trimodal therapy (TMT) for muscle invasive bladder cancer (MIBC) shows comparable results to radical cystectomy in carefully selected patients, suggesting it is a promising bladder preservation treatment.

A multidisciplinary team approach is essential for managing patients undergoing TMT, and future research aims to incorporate immunotherapy into this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder Preservation Therapy: Review of Literature and Future Directions of Trimodal Therapy. El-Achkar, A., Souhami, L., Kassouf, W.[2018]

In a study of 136 muscle-invasive bladder cancer patients treated with bladder-sparing trimodality therapy, higher immune infiltration was linked to better disease-specific survival, suggesting that immune signatures could help predict treatment outcomes.

Conversely, a stromal signature was associated with worse disease-specific survival in patients who underwent neoadjuvant chemotherapy and radical cystectomy, indicating that different tumor microenvironments may respond differently to treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer. Efstathiou, JA., Mouw, KW., Gibb, EA., et al.[2020]

In a study of 303 patients treated with trimodality bladder-sparing therapy (TMT) for muscle-invasive urothelial cancer, variant urothelial carcinoma (VUC) showed a complete response rate of 82%, similar to the 83% in pure urothelial carcinoma (PUC), indicating that VUC responds well to TMT.

There were no significant differences in disease-specific survival (DSS) or overall survival (OS) between patients with VUC and those with PUC, suggesting that the presence of VUC should not disqualify patients from receiving TMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of Patients with Histologic Variants of Urothelial Cancer Treated with Trimodality Bladder-sparing Therapy. Krasnow, RE., Drumm, M., Roberts, HJ., et al.[2018]

In a study of 76 patients with muscle-invasive bladder cancer (MIBC) treated with trimodality therapy (TMT), ERCC2 mutations were identified as a significant biomarker for improved long-term response, with patients showing better bladder-intact event-free survival (mBI-EFS).

The presence of ERCC2 mutations not only correlated with favorable clinical outcomes but also indicated increased sensitivity to cisplatin and radiation treatment in laboratory tests, suggesting a potential mechanism for enhanced therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic Tumor Correlates of Clinical Outcomes Following Organ-Sparing Chemoradiation Therapy for Bladder Cancer. Kamran, SC., Zhou, Y., Otani, K., et al.[2023]

In a study of 17 patients with muscle invasive bladder cancer, nonadaptive magnetic resonance imaging-guided radiation therapy (MRgRT) for partial bladder boost (PBB) demonstrated a high local control rate of 92% over a median follow-up of 18.2 months, indicating its efficacy in bladder preservation.

The treatment showed favorable dosimetric parameters with low acute toxicity rates, as most patients experienced only mild to moderate genitourinary and gastrointestinal side effects, suggesting that MRgRT PBB is a safe and effective option for select patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trimodal Therapy Using an MR-guided Radiation Therapy Partial Bladder Tumor Boost in Muscle Invasive Bladder Cancer. Liveringhouse, C., Netzley, A., Bryant, JM., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40549384/

Cost-Effectiveness of Trimodal Therapy and Radical ... TMT was associated with improved quality of life but was not cost-effective relative to RC at 5 and 10 years given higher treatment costs.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2835469

Cost-Effectiveness of Trimodal Therapy and Radical ... In this economic evaluation study of TMT and RC for treatment of MIBC, TMT was associated with improved quality of life but was not cost-effective relative to ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1078143925000110

Trimodality therapy versus radical cystectomy for muscle- ... Our meta-analysis of studies of the next-highest quality of evidence suggests that RC may still confer OS and CSS benefit over TMT in MIBC.

4. e-juo.org e-juo.org/m/journal/view.php?number=599

Trimodal Therapy in the Treatment of Muscle-Invasive ... A study analyzing data from the US National Cancer Database on 32,300 bladder cancer patients found that 5-year OS was 48% for RC and 30% for ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.488

Comparative real-world survival outcomes of muscle ... Results: A total of 605 patients receiving TMT for MIBC were identified: 162 (26.8%) BO-CCRT and 443 (73.2%) WP-CCRT. The median follow-up time was 25.6 months ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7124184/

Outcomes of trimodality bladder-sparing therapy for muscle ... Conclusions. Our study supports the concept of curative bladder-sparing treatment of TMT in MIBC but given the median followup of 21 months, these findings ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S240545692400244X

Trimodality Therapy Versus Radical Cystectomy for Muscle ... So far, the reported outcomes are comparable with those of radical surgery, and we found no signs of excess toxicity.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9124076/

Comparing Long-Term Survival Outcomes for Muscle ... Our findings supported that MIBC patients with TMT yielded survival outcomes comparable to MIBC patients who underwent RC overall.

9. urotoday.com urotoday.com/conference-highlights/aua-2025/aua-2025-bladder-cancer/160129-aua-2025-is-tmt-really-a-valid-option-for-all-my-patients-with-mibc.html

AUA 2025: Is TMT Really a Valid Option for All My Patients ... Generally, the cystectomy rate in large series for trimodality therapy toxicity is 1-2%, and the lifetime risk of dying from a radiation therapy ...