Durvalumab And Radiation Therapy Followed by Adjuvant Durvalumab in Patients With Urothelial Cancer (T2-4 N0-2 M0) of the Bladder (DUART)
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|ClinicalTrials.gov Identifier: NCT02891161|
Recruitment Status : Active, not recruiting
First Posted : September 7, 2016
Last Update Posted : February 8, 2021
|Condition or disease||Intervention/treatment||Phase|
|Urothelial Cancer||Drug: durvalumab Radiation: Radiation Therapy||Phase 1 Phase 2|
OUTLINE: This is a multi-center study.
The phase Ib study will evaluate the safety of combining durvalumab with RT followed by adjuvant durvalumab. The phase II study will estimate the Progression Free Survival (PFS) and Disease Control Rate (DCR) with durvalumab plus RT followed by single agent durvalumab for patients with UC of bladder.
PHASE Ib INVESTIGATIONAL TREATMENT:
Cohort 1 will consist of up to 6 patients who will receive durvalumab 1500mg 2 doses Q4 weekly with RT to gross disease, 64.8 Gy, 36 fractions on weekdays over about 7 weeks. Durvalumab will be started on day 1; RT will be started on day 1 or 2.
Three patients will be enrolled initially. If 2 or more patients (out of 3) experience dose-limiting toxicity (DLT), the combined treatment will be considered unsafe. Otherwise, an additional 3 patients will be treated at the same dose. If 0 or 1 patient experience DLT, the dose of durvalumab will be deemed safe for phase 2 part of the study. If, however, 2 or more patients (out of 6) experience DLT, the combined treatment will be considered unsafe.
Post-concurrent durvalumab and RT, single agent durvalumab will be given1500mg every 4 weeks (±7 days) for a total period of up to 12 months. Adjuvant durvalumab treatment will be started 3-4 weeks post completion of durvalumab and RT.
PHASE II INVESTIGATIONAL TREATMENT:
Subjects will receive durvalumab 1500mg 2 doses Q4 weekly with RT to gross disease, 64.8 Gy, 36 fractions on weekdays over about 7 weeks. Durvalumab will start on Day 1. RT to start on Day 1 or 2.
Post-concurrent durvalumab and RT, single agent durvalumab will be given1500mg every 4 weeks (±7 days) for a total period of up to 12 months. Adjuvant durvalumab monotherapy will be started 3-4 weeks post completion of durvalumab and RT.
Life expectancy of >6 months per treating physician.
Adequate organ and marrow function as defined below:
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)
- Platelet count ≥ 100 x 10^9/L (>100,000 per mm^3)
- Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN.
- Serum creatinine CL>30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase Ib/II Study of Concurrent Durvalumab And Radiation Therapy (DUART) Followed by Adjuvant Durvalumab in Patients With Urothelial Cancer (T2-4 N0-2 M0) of the Bladder: Big Ten Cancer Research Consortium BTCRC-GU15-023|
|Study Start Date :||November 2016|
|Estimated Primary Completion Date :||March 2021|
|Estimated Study Completion Date :||March 2022|
Experimental: Arm A: Safety Run In Phase Ib
Subjects will receive durvalumab 1500mg Q4 weekly with RT to gross disease over 36 fractions. Durvalumab will start on Day 1. RT to start on Day 1 or 2. Subjects will receive adjuvant durvalumab monotherapy Q4 week, up to 12 months. Durvalumab monotherapy to start 4 weeks post completion of durvalumab and RT.
1500 mg Q4 weekly
Radiation: Radiation Therapy
64.8 Gy, 36 daily fractions on weekdays over about 7 weeks
Other Name: RT
Experimental: Arm B: Investigational Treatment Phase II
Subjects will receive durvalumab 1500mg Q4 weekly with RT to gross disease over 36 fractions. Durvalumab will start on Day 1. RT to start on Day 1 or 2.. Subjects will receive adjuvant durvalumab monotherapy Q4 week, up to 12 months. Adjuvant durvalumab monotherapy to start 4 weeks post completion of durvalumab and RT.
1500 mg Q4 weekly
- Safety Assessment - Evaluation of DLT (dose limiting toxicity) rate [ Time Frame: 6 months ]Assess the safety of combining durvalumab with RT in that DLT rate is lower than than 33% using CTCAE version 4.
- Progression Free Survival [ Time Frame: 1 year ]Progression free survival rate at one year is defined as the probability that a patient remains free of progression of disease (SD+CR+PR) by modified RECIST 1.1 and cystoscopy at 1 year from the start of durvalumab treatment, D1 of durvaRT.
- Disease Control Rate [ Time Frame: 15 months ]The disease control rate is the proportion of all subjects with stable disease (SD) for 8 weeks, or partial response (PR), or complete response (CR) according to modified RECIST 1.1 and cystoscopy, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).
- Complete Remission [ Time Frame: 2 years ]Estimate the rate of complete remission (CR) post durvaRT by modified RECIST 1.1
- Overall Survival [ Time Frame: 2 years ]Estimate the overall survival (OS), defined as time from start of treatment, D1, to the date of death due to any cause.
- Correlate the expression of PD-L1 on immunohistochemistry at pre-treatment and post- durvaRT treatment with DCR [ Time Frame: 2 years ]2. To correlate the expression of PD-L1 on immunohistochemistry at pre-treatment (TURBT specimen if possible) and post- durvaRT treatment (cystoscopy-biopsy 2-3 weeks post durvaRT) with DCR.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02891161
|United States, Iowa|
|University of Iowa Hospital and Clinics|
|Iowa City, Iowa, United States, 52242|
|United States, Nebraska|
|Nebraska Methodist Hospital|
|Omaha, Nebraska, United States, 68114|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08903|
|United States, New York|
|Montefiore Medical Center|
|Bronx, New York, United States, 10641|
|United States, Pennsylvania|
|Penn State Cancer Intsitute|
|Hershey, Pennsylvania, United States, 17033|
|United States, Wisconsin|
|University of Wisconsin|
|Madison, Wisconsin, United States, 53705|
|Froedtert & The Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|