Bladder Preservation for Patients With Muscle Invasive Bladder Cancer (MIBC) With Variant Histology

August 4, 2026 updated by: Leslie Ballas

IIT2023-13-BALLAS-VHTMT: Bladder Preservation for Patients With Muscle Invasive Bladder Cancer (MIBC) With Variant Histology

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Trimodal therapy (TMT) is accepted as an NCCN category 1 alternative to radical cystectomy (with neoadjuvant chemotherapy) in patients with cT2N0M0 muscle-invasive urothelial cell bladder cancer (MIBC). Not all patients with MIBC have pure urothelial cell carcinoma; urothelial carcinoma with variant histology (VH) described any morphologic variant of conventional urothelial carcinoma that is believed to be derived from urothelial carcinoma and is typically admixed with conventional urothelial carcinoma in the same tumor. Variant histologies described include squamous differentiation, glandular differentiation, micropapillary, sarcomatoid, small cell/neuroendocrine, plasmacytoid and nested variant. This is a rare tumor type and understudied. For patients with variant histologies there is limited data on the use of trimodal therapy. There are a couple single institution retrospective studies and data from the NCDB, but no prospective data.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars Sinai Medical Center
        • Principal Investigator:
          • Leslie Ballas, MD
        • Sub-Investigator:
          • Anirban Mitra, MD, PhD
        • Sub-Investigator:
          • Michael Ahdoor, MD
        • Sub-Investigator:
          • Charles Rosser, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Documented diagnosis of MIBC with variant histology, cT2-T4N0M0, confirmed by TURBT and CT C/A/P and/or PET.
  • Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

Exclusion Criteria:

  • Evidence of diffuse cis on pathology
  • Presence of bilateral hydronephrosis (if hydronephrosis is present, can only be unilateral)
  • Prior radiotherapy to the pelvis
  • History of systemic therapy for MIBS
  • Presence of concurrent cancer (remote history of cancer (>5 years) allowed if the patient is without evidence of disease)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Arm
Neoadjuvant chemotherapy followed by trimodal therapy consisting of TURBT followed by concurrent chemotherapy with radiation therapy
Drug: Trimodal therapy (TMT) within 45 days of neoadjuvant chemotherapy (NAC)
Single-arm, open-label

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of initiating TMT
Time Frame: 45 days
To evaluate the feasibility of initiating TMT within 45 days of completion of NAC - Feasibility will be defined as at least 17 study participants initiating TMT within 45 days of NAC
45 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3-year bladder intact event free survival (BIEFS)
Time Frame: 3 year
To estimate 3-year bladder intact event free survival (BIEFS) in patients undergoing TMT for MIBC with VH-TMT
3 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free (<=T2) survival rates
Time Frame: 3 year
To estimate progression free (<=T2) survival rates from TMT
3 year
Metastasis-free survival
Time Frame: 3 year
To estimate the metastasis-free survival of TMT
3 year
Rate of salvage cystectomy
Time Frame: 3 year
To estimate the rate of salvage cystectomy following TMT
3 year
Blood and urine correlatives of clinical outcomes
Time Frame: 3 year
To investigate blood and urine correlatives of clinical outcomes (Signatera and Oncuria)
3 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leslie Ballas

Investigators

  • Principal Investigator: Leslie Ballas, MD, Cedars-Sinai Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 16, 2026

Primary Completion (Estimated)

December 1, 2030

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

May 13, 2024

First Submitted That Met QC Criteria

May 13, 2024

First Posted (Actual)

May 16, 2024

Study Record Updates

Last Update Posted (Actual)

August 6, 2026

Last Update Submitted That Met QC Criteria

August 4, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT2023-13-BALLAS-VHTMT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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