A Phase II Multicenter Study of Chemotherapy Versus Chemotherapy Plus Durvalumab (MEDI 4736) in Patients With Lymph Node Positive Urothelial Carcinoma of the Bladder
brief summary
This is a phase II randomized study of standard of care (SOC) neo-adjuvant cisplatin chemotherapy (NAC) versus NAC plus durvalumab in patients with either clinical or pathologic intra-pelvic node-positive urothelial carcinoma of the bladder. Patients with cTanyN1-3M0 via American Joint Committee on Cancer (AJCC) 8th edition staging30 will be considered tor enrollment in this trial. We plan to enroll 60 patients. Patients will be randomized 2:1 to the intervention arm with durvalumab plus NAC vs SOC NAC. In patients randomized to receive, durvalumab will be continued as maintenance every 4 weeks until either relapse or 1 year, whichever event occurs first. Tissue collection will occur as a biopsy prior to initiation of neo-adjuvant therapy via both transurethral biopsy of bladder and lymph node biopsy. Tissue will again be collected at the time of radical cystectomy or, in patients who are no longer surgical candidates, in the form of biopsy as standard of care. Blood and urine will be collected at baseline, week 2, week 6, week 16, and at the 6 week-post surgery visit for analysis of correlative studies.
detailed description
Primary Objective:
• To estimate the difference in pathologic complete response rate as defined as no evidence of disease (ypT0N0) or carcinoma in situ within the bladder only (ypTcisN0) in patients after administration of the combination of dose-dense MVAC and durvalumab versus dose-dense MVAC alone.
Secondary Objectives:
* To estimate the difference in the rate of patients eligible for surgical consolidation within 90 days of completion of pre-surgical treatment. * To estimate the difference in the proportion of patients with relapse free survival at 12 and 36 months following surgery in each treatment arm. * To estimate the difference in overall survival for both arms on study. * To measure lymph node response with those with measurable disease via RECIST v1.1 criteria at baseline, week 6, and week 12 on study. * To evaluate the toxicity of the combination of dose-dense MVAC chemotherapy and durvalumab.
Correlative Objectives:
• Exploratory biomarkers to study the correlation between immunological and molecular changes in tumor tissues and peripheral blood with pathologic complete response, time until relapse and rate of adverse events, with a specific emphasis upon comparison of tissue samples in patients exposed to combination dose-dense MVAC and durvalumab versus dose-dense MVAC alone
official title
Durvalumab and Standard Chemotherapy for the Treatment of Lymph Node Positive Bladder Cancer