This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of combining durvalumab ± tremelimumab with standard of care (SoC) chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) followed by durvalumab monotherapy versus SoC alone as first-line chemotherapy in patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,246
Durvalumab IV (intravenous infusion)
Tremelimumab IV (intravenous infusion)
Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.
Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.
Research Site
Birmingham, Alabama, United States
Research Site
Bakersfield, California, United States
Research Site
Fullerton, California, United States
Research Site
Los Angeles, California, United States
Research Site
Salinas, California, United States
Research Site
Overall Survival (OS)
OS is defined as the time from the date of randomization until death due to any cause
Time frame: approximately 5 years
Overall Survival (OS)
Additional analysis beyond the primary endpoint
Time frame: approximately 5 years
Overall Survival at 24 months (OS24)
The OS24 will be defined as the Kaplan-Meier estimate of OS at 24 months
Time frame: 24 months
Progression Free Survival (PFS)
PFS (per RECIST 1.1) will be defined as the time from the date of randomization until the date of first objective disease progression or death
Time frame: approximately 5 years
Alive and Progression Free Survival at 12 months (APF12)
The APF12 will be defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1) at 12 months
Time frame: 12 months
Objective Response Rate (ORR)
ORR (per RECIST 1.1) is defined as the number (%) of patients with at least 1 visit response of complete response or partial response and will be based on a subset of all randomized patients
Time frame: approximately 5 years
Duration of Response (DoR)
DoR (per RECIST 1.1) will be defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression
Time frame: approximately 5 years
Disease Control Rate (DCR)
DCR is defined as the proportion of subjects with the best overall response of complete response, partial response or stable disease per RECIST 1.1
Time frame: approximately 5 years
Time from randomization to second (PFS2)
PFS2 will be defined as the time from the date of randomization to the earliest of the progression events subsequent to that used for the PFS endpoint or death
Time frame: approximately 5 years
To assess disease-related symptoms, physical functioning, and other Health-related quality of life
Collection of patient reported outcome questionnaires
Time frame: approximately 5 years
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Santa Barbara, California, United States
Research Site
Truckee, California, United States
Research Site
New Haven, Connecticut, United States
Research Site
Washington D.C., District of Columbia, United States
Research Site
Orlando, Florida, United States
...and 212 more locations