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

Trial Summary

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.

What data supports the effectiveness of the treatment Trimodal Therapy (TMT) for muscle invasive bladder cancer?

Research shows that trimodal therapy (TMT), which combines surgery, chemotherapy, and radiation, is an effective alternative to removing the bladder for treating muscle-invasive bladder cancer. Studies highlight its role in preserving the bladder while providing similar survival outcomes to more invasive surgery. ^{1 2 3 4 5}

Is trimodal therapy (TMT) safe for humans?

Trimodal therapy (TMT) for bladder preservation in muscle-invasive bladder cancer has been studied and is considered an acceptable treatment for selected patients, suggesting it is generally safe for humans. ^{1 2 3 5 6}

How is the treatment Trimodal Therapy (TMT) different from other treatments for muscle invasive bladder cancer?

Trimodal Therapy (TMT) is unique because it combines three approaches: surgery to remove as much of the tumor as possible, followed by chemotherapy and radiation therapy. This approach aims to preserve the bladder, offering an alternative to radical cystectomy (complete removal of the bladder), which is the standard treatment for muscle-invasive bladder cancer. ^{1 3 4 5 6}

What is the purpose of this trial?

This is a Phase II, single cohort study designed to evaluate outcomes in patients with muscle invasive bladder cancer (MIBC) with variant histology who receive neoadjuvant chemotherapy (NAC) with or without immunotherapy (IO) followed by trimodal therapy (TMT). Enrolled patients will undergo at least 3 cycles of NAC +/- IO (oncologist's choice) followed by a four- or six-week course of concurrent standard of care chemotherapy and radiation therapy. These patients will be compared with historical controls of patients with a diagnosis of pure urothelial carcinoma who have undergone TMT. This study has been designed to test the hypothesis that variant histology TMT can be delivered within 45 days of NAC +/- IO and is therefore a viable option in patients who are risk of systemic disease spread.

Research Team

Leslie Ballas

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

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 no current cancer or a past cancer that was over 5 years ago with no signs of it now.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

References

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

Trimodal Therapy Using an MR-guided Radiation Therapy Partial Bladder Tumor Boost in Muscle Invasive Bladder Cancer. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Muscle-invasive bladder cancer organ-preserving therapy: systematic review and meta-analysis. [2019]

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

Bladder Preservation Therapy: Review of Literature and Future Directions of Trimodal Therapy. [2018]

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

Genomic Tumor Correlates of Clinical Outcomes Following Organ-Sparing Chemoradiation Therapy for Bladder Cancer. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of Patients with Histologic Variants of Urothelial Cancer Treated with Trimodality Bladder-sparing Therapy. [2018]