About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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
Trial design
Single group
Treatments tested in this trial
Trimodal therapy (TMT) within 45 days of neoadjuvant chemotherapy (NAC)
DrugSingle-arm, open-label
Treatment groups
Trial outcomes
Primary outcomes
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
Secondary outcomes
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
Other outcomes
Progression free (<=T2) survival rates
To estimate progression free (\<=T2) survival rates from TMT
Metastasis-free survival
To estimate the metastasis-free survival of TMT
Rate of salvage cystectomy
To estimate the rate of salvage cystectomy following TMT
Blood and urine correlatives of clinical outcomes
To investigate blood and urine correlatives of clinical outcomes (Signatera and Oncuria)
Sponsors and contacts
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Leslie Ballas
Lead sponsor
Cedars-Sinai Medical Center
Sponsor institution