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

NCT ID: NCT06417190

Last Updated: 2026-02-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-16
• Study Completion Date: 2030-12-31

Brief Summary

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.

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.

Conditions

Muscle-Invasive Bladder Carcinoma; Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm

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

Group Type: EXPERIMENTAL

Trimodal therapy (TMT) within 45 days of neoadjuvant chemotherapy (NAC)

Intervention Type: DRUG

Single-arm, open-label

Interventions

Trimodal therapy (TMT) within 45 days of neoadjuvant chemotherapy (NAC)

Single-arm, open-label

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Leslie Ballas

OTHER

Sponsor Role: lead

Responsible Party

Leslie Ballas

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Leslie Ballas, MD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Clinical Trial Navigator

Role: CONTACT

cancer.trial.info@cshs.org

3104232133

Facility Contacts

Clinical Trial Recruitment Navigator

Role: primary

cancer.trial.info@cshs.org

3104232133

Other Identifiers

IIT2023-13-BALLAS-VHTMT

Identifier Type: -

Identifier Source: org_study_id