Muscle-Invasive Bladder Carcinoma, Tumor
Conditions
Keywords
Trimodal Therapy (TMT), Neoadjuvant Chemotherapy, muscle-invasive urothelial cell bladder cancer (MIBC)
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.
Interventions
DRUGTrimodal therapy (TMT) within 45 days of neoadjuvant chemotherapy (NAC)
Single-arm, open-label
Sponsors
Leslie Ballas
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of initiating TMT | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3-year bladder intact event free survival (BIEFS) | 3 year | To estimate 3-year bladder intact event free survival (BIEFS) in patients undergoing TMT for MIBC with VH-TMT |
Countries
United States
Contacts
CONTACTClinical Trial Navigator
PRINCIPAL_INVESTIGATORLeslie Ballas, MD
Cedars-Sinai Medical Center
Outcome results
None listed