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

Official title

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

Overview

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.

Interventions

• Drug Trimodal therapy (TMT) within 45 days of neoadjuvant chemotherapy (NAC)
  Single-arm, open-label

Primary outcome measures

• Feasibility of initiating TMT [Time frame: 45 days]

Secondary outcome measures (1)

• 3-year bladder intact event free survival (BIEFS) [Time frame: 3 year]

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Cedars Sinai Medical Center — Los Angeles

Identifiers

NCT: NCT06417190 · IIT2023-13-BALLAS-VHTMT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗