Unresectable Locally Advanced Urothelial CancerPhase 3NILENCT03682068
Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer
A Phase 3 study testing Durvalumab, Tremelimumab and Cisplatin + Gemcitabine in people with Unresectable Locally Advanced Urothelial Cancer and Metastatic Urothelial Cancer, run by AstraZeneca at 222 sites in 22 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Unresectable Locally Advanced Urothelial Cancer, Metastatic Urothelial Cancer
- What is being tested?
- Durvalumab, Tremelimumab and Cisplatin + Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,246 participants
- Where
- 222 sitesin 22 countries
- Study dates
- 27 Sep 2018to 1 Jun 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Prior exposure to immune-mediated therapy (with exclusion of Bacillus Calmette Guerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, or anti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
- 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
Trial locations and contacts
222 sites in 22 countries.
222 sites in 22 countries
China27 sites
Research Site
Beijing, 100034
Research Site
Beijing, 100191
Research Site
Beijing, 100730
Research Site
Changchun, 130021
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Changsha, 410008
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Changsha, 410013
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Chongqing, 400038
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Chongqing, 400042
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Dalian, 116027
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Guangzhou, 510000
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Guangzhou, 510060
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Hangzhou, 310003
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Hangzhou, 310009
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Hangzhou, 310014
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Hangzhou, 310022
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Jinan, 250012
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Nanchang, 330006
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Nanjing, 2100008
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Shanghai, 200032
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Shanghai, 200072
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Shenyang, 110001
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Suzhou, 215006
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Tianjin, 300211
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Tianjin
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Ürümqi, 830000
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Wuhan, 430022
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Xi'an, 710061
Japan24 sites
Research Site
Bunkyō City, 113-8603
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Chūōku, 104-0045
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Fukuoka, 811-1347
Research Site
Hirosaki-shi, 036-8563
Research Site
Kanazawa, 920-8641
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Kita-gun, 761-0793
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Koshigaya-shi, 343-8555
Research Site
Kōtoku, 135-8550
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Kumamoto, 860-0008
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Kumamoto, 860-8556
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Kyoto, 606-8507
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Miyazaki, 889-1692
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Nagasaki, 852-8501
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Nagoya, 466-8560
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Nagoya, 467-0001
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Niigata, 951-8520
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Osaka, 541-8567
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Osaka, 545-8586
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Osakasayama-shi, 589-8511
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Shinjuku-ku, 160-8582
Research Site
Suita-shi, 565-0871
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Toyama, 930-0194
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Yokohama, 232-0024
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Yokohama, 241-8515
United States23 sites
Research Site
Bakersfield, California, 93309
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Birmingham, Alabama, 35294
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Bozeman, Montana, 59715
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Chicago, Illinois, 60611
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Fort Wayne, Indiana, 46804
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Fort Worth, Texas, 76104
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Fullerton, California, 92835
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Germantown, Tennessee, 38138
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Grand Rapids, Michigan, 49503
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Kansas City, Kansas, 66160
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Los Angeles, California, 90024
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Louisville, Kentucky, 40202
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New Haven, Connecticut, 06520
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New Hyde Park, New York, 11042
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New Orleans, Louisiana, 70112
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New York, New York, 10029
Research Site
New York, New York, 10065
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Orlando, Florida, 32806
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Rochester, New York, 14642
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Salinas, California, 93901
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Santa Barbara, California, 93105
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Truckee, California, 96161
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Washington D.C., District of Columbia, 20007
Russia15 sites
Research Site
Ivanovo, 153040
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Krasnoyarsk, 660133
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Moscow, 105077
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Moscow, 105229
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Moscow, 115280
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Moscow, 125284
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Nizhny Novgorod, 603074
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Nizhny Novgorod, 603137
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Omsk, 644013
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Rostov-on-Don, 344037
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Saint Petersburg, 195067
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Saint Petersburg, 197758
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Saint Petersburg, 199178
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Tyumen, 625041
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Vologda, 160012
Brazil13 sites
Research Site
Curitiba, 80810-050
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Fortaleza, 60336-232
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Porto Alegre, 90020-090
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Porto Alegre, 90610-000
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Porto Alegre, 91350-200
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Ribeirão Preto, 14048-900
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Rio de Janeiro, 20231-050
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Rio de Janeiro, 22793-080
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Salvador, 41.950-610
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Santa Maria, 97015-450
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São José do Rio Preto, 15090-000
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São Paulo, 01246-000
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São Paulo, 01327-001
Italy10 sites
Research Site
Arezzo, 52100
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Milan, 20132
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Milan, 20133
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Naples, 80131
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Orbassano, 10043
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Parma, 43126
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Pavia, 27100
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Roma, 00100
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Terni, 05100
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Verona, 37134
Spain10 sites
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Barcelona, 08908
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Barcelona, 8003
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Barcelona, 8035
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Lugo, 27003
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Madrid, 28007
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Madrid, 28034
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Madrid, 28040
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Málaga, 29010
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Santander, 39008
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Seville, 41013
India9 sites
Research Site
Gūrgaon, 122001
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Hubli, 580025
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Kolkata, 700160
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Mysuru, 570017
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Nagpur, 440012
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Nashik, 422005
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New Delhi, 110085
Research Site
New Delhi, 11029
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Pune, 411004
Poland9 sites
Research Site
Bialystok, 15-027
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Gdansk, 80-952
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Grudziądz, 86-300
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Koszalin, 75-581
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Krakow, 31-501
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Olsztyn, 10-228
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Poznan, 60-693
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Radom, 26-600
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Warsaw, 02-781
Australia8 sites
Research Site
Box Hill, 3128
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Elizabeth Vale, 5112
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Kogarah, 2217
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Macquarie University, 2109
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Murdoch, 6150
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Orange, 2800
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South Brisbane, 4101
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St Albans, 3021
Philippines8 sites
Research Site
Bacolod, 6100
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Baguio City, 2600
Research Site
Cebu, 6000
Research Site
Davao City, 8000
Research Site
Makati, 1229
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Manila, 1015
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Quezon City, 1101
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Quezon City, 1104
Bulgaria7 sites
Research Site
Pleven, 5800
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Plovdiv, 4000
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Sofia, 1303
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Sofia, 1431
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Sofia, 1527
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Sofia, 1797
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Varna, 9010
Canada7 sites
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Calgary, Alberta, T2N 5G2
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Edmonton, Alberta, T6G 1Z2
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Hamilton, Ontario, L8V 5C2
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Montreal, Quebec, H3T 1E2
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Ottawa, Ontario, K1H 8L6
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Toronto, Ontario, M5G IX6
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Vancouver, British Columbia, V5Z 4E6
Czechia7 sites
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Brno, 656 91
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Hradec Králové, 500 05
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Olomouc, 77900
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Ostrava, 708 52
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Prague, 128 08
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Prague, 140 59
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Prague, 180 81
Hungary7 sites
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Budapest, 1062
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Budapest, 1122
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Budapest, 1145
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Debrecen, 4032
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Győr, 9024
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Kecskemét, 6000
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Szolnok, 5000
South Korea7 sites
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Goyang-si, 10408
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Incheon, 21565
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Seoul, 02841
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Seoul, 03722
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Seoul, 05505
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Seoul, 06351
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Suwon, 16247
Taiwan6 sites
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Taichung, 404
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Taichung, 40705
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Tainan, 704
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Taipei, 10050
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Taipei, 11217
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Taoyuan, 333
Turkey (Türkiye)6 sites
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Adana, 1260
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Adapazarı, 54290
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Ankara, 06590
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Edirne, 22030
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Istanbul, 34030
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Izmir
Argentina5 sites
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Ciudad de Buenos Aires, 1280
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Ciudad de Buenos Aires, C1120AAT
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Ciudad de Buenos Aires, C1419AHL
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Ciudad de Buenos Aires, C1426ANZ
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Rosario, S2000DEJ
Israel5 sites
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Haifa, 31096
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Jerusalem, 91120
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Kfar Saba, 95847
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Petah Tikva, 4941492
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Ramat Gan, 52621
Thailand5 sites
Research Site
Bangkok, 10300
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Bangkok, 10400
Research Site
Khon Kaen, 40002
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Mueang, 50200
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Songkhla, 90110
Vietnam4 sites
Research Site
Hà Nội, 100000
Research Site
Hanoi, 100000
Research Site
Hanoi, 10000
Research Site
Ho Chi Minh City, 70000
About this study
Official title: 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.
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).
- Being tested
- Durvalumab, Tremelimumab, Cisplatin + Gemcitabine, Carboplatin + Gemcitabine
- Keywords
- renal pelvis, ureters, urinary bladder, urethra, bladder cancer
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736
Durvalumab IV (intravenous infusion)
TremelimumabDrug
Tremelimumab IV (intravenous infusion)
Cisplatin + GemcitabineDrug
Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.
Carboplatin + GemcitabineDrug
Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab in Combination with SoC Chemotherapy | Experimental | Durvalumab 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 Receives: Drug: Durvalumab; Drug: Cisplatin + Gemcitabine; Drug: Carboplatin + Gemcitabine |
| Durvalumab in Combination with Tremelimumab+SoC Chemotherapy | Experimental | Durvalumab 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 Receives: Drug: Durvalumab; Drug: Tremelimumab; Drug: Cisplatin + Gemcitabine; Drug: Carboplatin + Gemcitabine |
| SoC Chemotherapy | Active comparator | 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 Receives: Drug: Cisplatin + Gemcitabine; Drug: Carboplatin + Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
OS is defined as the time from the date of randomization until death due to any cause
Measured: approximately 5 years
Secondary outcomes (9)
Overall Survival (OS)
Additional analysis beyond the primary endpoint
Measured: approximately 5 years
Overall Survival at 24 months (OS24)
The OS24 will be defined as the Kaplan-Meier estimate of OS at 24 months
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: approximately 5 years
To assess disease-related symptoms, physical functioning, and other Health-related quality of life
Collection of patient reported outcome questionnaires
Measured: approximately 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2018
- Study start27 Sep 2018
- Primary completion1 Jun 2026
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Unresectable Locally Advanced Urothelial CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,246 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03682068
- Sponsor's protocol ID
- D933SC00001
- Other IDs
- 2018-001883-48, 2018
- Acronym
- NILE
- Status last verified
- Jul 2026
- First submitted
- 6 Sep 2018
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Mamede I, Escalante-Romero L, Celso DSG, Reis PCA, Dacoregio MI, Alves AC, Stecca C. Immunotherapy Plus Chemotherapy Versus Chemotherapy Alone as First-Line Treatment for Advanced Urothelial Cancer: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials. Clin Genitourin Cancer. 2024 Oct;22(5):102154. doi: 10.1016/j.clgc.2024.102154. Epub 2024 Jul 11.
PubMed 39094286