Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer
NILE
A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line Durvalumab in Combination With Standard of Care Chemotherapy and Durvalumab in Combination With Tremelimumab and Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone in Patients With Unresectable Locally Advanced or Metastatic Urothelial Cancer.
2 other identifiers
interventional
1,246
22 countries
222
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Sep 2018
Longer than P75 for phase_3
222 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 6, 2018
CompletedFirst Posted
Study publicly available on registry
September 24, 2018
CompletedStudy Start
First participant enrolled
September 27, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 29, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
April 29, 2026
CompletedFebruary 3, 2026
January 1, 2026
7.6 years
September 6, 2018
January 30, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS)
OS is defined as the time from the date of randomization until death due to any cause
approximately 5 years
Secondary Outcomes (9)
Overall Survival (OS)
approximately 5 years
Overall Survival at 24 months (OS24)
24 months
Progression Free Survival (PFS)
approximately 5 years
Alive and Progression Free Survival at 12 months (APF12)
12 months
Objective Response Rate (ORR)
approximately 5 years
- +4 more secondary outcomes
Other Outcomes (3)
To assess safety using a summary of adverse events.
approximately 5 years
To assess pharmacokinetics of Durvalumab and Tremelimumab
approximately 5 years
To assess immunogenicity of Durvalumab and Tremelimumab
approximately 5 years
Study Arms (3)
Durvalumab in Combination with SoC Chemotherapy
EXPERIMENTALDurvalumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine
Durvalumab in Combination with Tremelimumab+SoC Chemotherapy
EXPERIMENTALDurvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks Tremelimumab will be provided for 4 cycles. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine
SoC Chemotherapy
ACTIVE COMPARATORPatients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine
Interventions
Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.
Durvalumab IV (intravenous infusion)
Tremelimumab IV (intravenous infusion)
Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.
Eligibility Criteria
You may qualify if:
- Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
- Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred \>12 months from the last therapy \[for chemoradiation and adjuvant treatment\] or \>12 months from the last surgery \[for neoadjuvant treatment\].
- At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
- World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
- Adequate organ and marrow function as defined in the protocol
- Life expectancy ≥12 weeks in the opinion of the investigator
- Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.
You may not qualify if:
- No severe concomitant condition that requires immunosuppression medication
- Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
- Patients who may be eligible for or are being considered for radical resection during the course of the study.
- Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (222)
Research Site
Birmingham, Alabama, 35294, United States
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Bakersfield, California, 93309, United States
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Fullerton, California, 92835, United States
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Los Angeles, California, 90095, United States
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Salinas, California, 93901, United States
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Santa Barbara, California, 93105, United States
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Truckee, California, 96161, United States
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New Haven, Connecticut, 06520, United States
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Washington D.C., District of Columbia, 20007, United States
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Orlando, Florida, 32806, United States
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Chicago, Illinois, 60611, United States
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Fort Wayne, Indiana, 46804, United States
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Kansas City, Kansas, 66160, United States
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Louisville, Kentucky, 40202, United States
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New Orleans, Louisiana, 70112, United States
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Grand Rapids, Michigan, 49503, United States
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Bozeman, Montana, 59715, United States
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New Hyde Park, New York, 11042, United States
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New York, New York, 10029, United States
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New York, New York, 10065, United States
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Rochester, New York, 14642, United States
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Germantown, Tennessee, 38138, United States
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Fort Worth, Texas, 76104, United States
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Ciudad de Buenos Aires, 1280, Argentina
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Ciudad de Buenos Aires, C1120AAT, Argentina
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Ciudad de Buenos Aires, C1419AHL, Argentina
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Ciudad de Buenos Aires, C1426ANZ, Argentina
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Rosario, S2000DEJ, Argentina
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Box Hill, 3128, Australia
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Elizabeth Vale, 5112, Australia
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Kogarah, 2217, Australia
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Macquarie University, 2109, Australia
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Murdoch, 6150, Australia
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Orange, 2800, Australia
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South Brisbane, 4101, Australia
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St Albans, 3021, Australia
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Curitiba, 80810-050, Brazil
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Fortaleza, 60336-232, Brazil
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Porto Alegre, 90020-090, Brazil
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Porto Alegre, 90610-000, Brazil
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Porto Alegre, 91350-200, Brazil
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Ribeirão Preto, 14048-900, Brazil
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Rio de Janeiro, 20231-050, Brazil
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Rio de Janeiro, 22793-080, Brazil
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Salvador, 41.950-610, Brazil
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Santa Maria, 97015-450, Brazil
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São José do Rio Preto, 15090-000, Brazil
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São Paulo, 01246-000, Brazil
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São Paulo, 01327-001, Brazil
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Pleven, 5800, Bulgaria
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Plovdiv, 4000, Bulgaria
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Sofia, 1303, Bulgaria
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Sofia, 1431, Bulgaria
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Sofia, 1527, Bulgaria
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Sofia, 1797, Bulgaria
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Varna, 9010, Bulgaria
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Calgary, Alberta, T2N 5G2, Canada
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Edmonton, Alberta, T6G 1Z2, Canada
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Vancouver, British Columbia, V5Z 4E6, Canada
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Hamilton, Ontario, L8V 5C2, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Toronto, Ontario, M5G IX6, Canada
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Montreal, Quebec, H3T 1E2, Canada
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Beijing, 100034, China
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Beijing, 100191, China
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Beijing, 100730, China
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Changchun, 130021, China
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Changsha, 410008, China
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Changsha, 410013, China
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Chongqing, 400038, China
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Chongqing, 400042, China
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Dalian, 116027, China
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Guangzhou, 510000, China
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Guangzhou, 510060, China
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Hangzhou, 310003, China
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Hangzhou, 310009, China
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Hangzhou, 310014, China
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Hangzhou, 310022, China
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Jinan, 250012, China
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Nanchang, 330006, China
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Nanjing, 2100008, China
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Shanghai, 200032, China
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Shanghai, 200072, China
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Shenyang, 110001, China
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Suzhou, 215006, China
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Tianjin, 300211, China
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Tianjin, China
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Ürümqi, 830000, China
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Wuhan, 430022, China
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Xi'an, 710061, China
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Brno, 656 91, Czechia
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Hradec Králové, 500 05, Czechia
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Olomouc, 77900, Czechia
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Ostrava, 708 52, Czechia
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Prague, 128 08, Czechia
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Prague, 140 59, Czechia
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Prague, 180 81, Czechia
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Budapest, 1062, Hungary
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Budapest, 1122, Hungary
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Budapest, 1145, Hungary
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Debrecen, 4032, Hungary
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Győr, 9024, Hungary
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Kecskemét, 6000, Hungary
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Szolnok, 5000, Hungary
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Gūrgaon, 122001, India
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Hubli, 580025, India
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Kolkata, 700160, India
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Mysuru, 570017, India
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Nagpur, 440012, India
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Nashik, 422005, India
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New Delhi, 110085, India
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New Delhi, 11029, India
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Pune, 411004, India
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Haifa, 31096, Israel
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Jerusalem, 91120, Israel
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Kfar Saba, 95847, Israel
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Petah Tikva, 4941492, Israel
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Ramat Gan, 52621, Israel
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Arezzo, 52100, Italy
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Milan, 20132, Italy
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Milan, 20133, Italy
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Naples, 80131, Italy
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Orbassano, 10043, Italy
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Parma, 43126, Italy
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Pavia, 27100, Italy
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Roma, 00100, Italy
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Terni, 05100, Italy
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Verona, 37134, Italy
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Bunkyō City, 113-8603, Japan
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Chūōku, 104-0045, Japan
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Fukuoka, 811-1347, Japan
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Hirosaki-shi, 036-8563, Japan
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Kanazawa, 920-8641, Japan
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Kita-gun, 761-0793, Japan
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Koshigaya-shi, 343-8555, Japan
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Kōtoku, 135-8550, Japan
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Kumamoto, 860-0008, Japan
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Kumamoto, 860-8556, Japan
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Kyoto, 606-8507, Japan
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Miyazaki, 889-1692, Japan
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Nagasaki, 852-8501, Japan
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Nagoya, 466-8560, Japan
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Nagoya, 467-0001, Japan
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Niigata, 951-8520, Japan
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Osaka, 541-8567, Japan
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Osaka, 545-8586, Japan
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Osakasayama-shi, 589-8511, Japan
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Shinjuku-ku, 160-8582, Japan
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Suita-shi, 565-0871, Japan
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Toyama, 930-0194, Japan
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Yokohama, 232-0024, Japan
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Yokohama, 241-8515, Japan
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Bacolod, 6100, Philippines
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Baguio City, 2600, Philippines
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Cebu, 6000, Philippines
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Davao City, 8000, Philippines
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Makati, 1229, Philippines
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Manila, 1015, Philippines
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Quezon City, 1101, Philippines
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Quezon City, 1104, Philippines
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Bialystok, 15-027, Poland
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Gdansk, 80-952, Poland
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Grudziądz, 86-300, Poland
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Koszalin, 75-581, Poland
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Krakow, 31-501, Poland
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Olsztyn, 10-228, Poland
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Poznan, 60-693, Poland
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Radom, 26-600, Poland
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Warsaw, 02-781, Poland
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Ivanovo, 153040, Russia
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Krasnoyarsk, 660133, Russia
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Moscow, 105077, Russia
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Moscow, 105229, Russia
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Moscow, 115280, Russia
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Moscow, 125284, Russia
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Nizhny Novgorod, 603074, Russia
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Nizhny Novgorod, 603137, Russia
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Omsk, 644013, Russia
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Rostov-on-Don, 344037, Russia
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Saint Petersburg, 195067, Russia
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Saint Petersburg, 197758, Russia
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Saint Petersburg, 199178, Russia
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Tyumen, 625041, Russia
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Vologda, 160012, Russia
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Goyang-si, 10408, South Korea
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Incheon, 21565, South Korea
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Seoul, 02841, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06351, South Korea
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Suwon, 16247, South Korea
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Barcelona, 08908, Spain
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Barcelona, 8003, Spain
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Barcelona, 8035, Spain
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Lugo, 27003, Spain
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Madrid, 28007, Spain
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Madrid, 28034, Spain
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Madrid, 28040, Spain
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Málaga, 29010, Spain
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Santander, 39008, Spain
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Seville, 41013, Spain
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Taichung, 404, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 704, Taiwan
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Taipei, 10050, Taiwan
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Taipei, 11217, Taiwan
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Taoyuan District, 333, Taiwan
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Bangkok, 10300, Thailand
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Bangkok, 10400, Thailand
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Khon Kaen, 40002, Thailand
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Mueang, 50200, Thailand
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Songkhla, 90110, Thailand
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Adana, 1260, Turkey (Türkiye)
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Adapazarı, 54290, Turkey (Türkiye)
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Ankara, 06590, Turkey (Türkiye)
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Edirne, 22030, Turkey (Türkiye)
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Istanbul, 34030, Turkey (Türkiye)
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Izmir, Turkey (Türkiye)
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Hanoi, 100000, Vietnam
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Hanoi, 10000, Vietnam
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Hà Nội, 100000, Vietnam
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Ho Chi Minh City, 70000, Vietnam
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 6, 2018
First Posted
September 24, 2018
Study Start
September 27, 2018
Primary Completion
April 29, 2026
Study Completion
April 29, 2026
Last Updated
February 3, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.