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

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: Not yet recruiting
• Conditions: Muscle-Invasive Bladder Carcinoma; Tumor
• Intervention / Treatment: Drug: Trimodal therapy (TMT) within 45 days of neoadjuvant chemotherapy (NAC)

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

• Study Contact: Name: Clinical Trial Navigator; Phone Number: 3104232133; Email: cancer.trial.info@cshs.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
      • Contact: Clinical Trial Recruitment Navigator; Phone Number: 310-423-2133; Email: cancer.trial.info@cshs.org
      • Principal Investigator: Leslie Ballas, MD
      • Sub-Investigator: Anirban Mitra, MD, PhD
      • Sub-Investigator: Michael Ahdoor, MD
      • Sub-Investigator: Charles Rosser, MD

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

1

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 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): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Neoadjuvant Chemotherapy; Trimodal Therapy (TMT); muscle-invasive urothelial cell bladder cancer (MIBC)
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms
• 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