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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03682068




Registration number
NCT03682068
Ethics application status
Date submitted
6/09/2018
Date registered
24/09/2018

Titles & IDs
Public title
Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer
Scientific 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.
Secondary ID [1] 0 0
2018-001883-48
Secondary ID [2] 0 0
D933SC00001
Universal Trial Number (UTN)
Trial acronym
NILE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unresectable Locally Advanced Urothelial Cancer 0 0
Metastatic Urothelial Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Durvalumab
Treatment: Drugs - Tremelimumab
Treatment: Drugs - Cisplatin + Gemcitabine
Treatment: Drugs - Carboplatin + Gemcitabine

Experimental: Durvalumab in Combination with SoC Chemotherapy - 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

Experimental: Durvalumab in Combination with Tremelimumab+SoC Chemotherapy - 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

Active comparator: SoC Chemotherapy - 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


Treatment: Drugs: Durvalumab
Durvalumab IV (intravenous infusion)

Treatment: Drugs: Tremelimumab
Tremelimumab IV (intravenous infusion)

Treatment: Drugs: Cisplatin + Gemcitabine
Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Treatment: Drugs: Carboplatin + Gemcitabine
Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
approximately 5 years
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
approximately 5 years
Secondary outcome [2] 0 0
Overall Survival at 24 months (OS24)
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Progression Free Survival (PFS)
Timepoint [3] 0 0
approximately 5 years
Secondary outcome [4] 0 0
Alive and Progression Free Survival at 12 months (APF12)
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Objective Response Rate (ORR)
Timepoint [5] 0 0
approximately 5 years
Secondary outcome [6] 0 0
Duration of Response (DoR)
Timepoint [6] 0 0
approximately 5 years
Secondary outcome [7] 0 0
Disease Control Rate (DCR)
Timepoint [7] 0 0
approximately 5 years
Secondary outcome [8] 0 0
Time from randomization to second (PFS2)
Timepoint [8] 0 0
approximately 5 years
Secondary outcome [9] 0 0
To assess disease-related symptoms, physical functioning, and other Health-related quality of life
Timepoint [9] 0 0
approximately 5 years

Eligibility
Key inclusion criteria
Key

* 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.

Key
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Box Hill
Recruitment hospital [2] 0 0
Research Site - Elizabeth Vale
Recruitment hospital [3] 0 0
Research Site - Kogarah
Recruitment hospital [4] 0 0
Research Site - Macquarie University
Recruitment hospital [5] 0 0
Research Site - Murdoch
Recruitment hospital [6] 0 0
Research Site - Orange
Recruitment hospital [7] 0 0
Research Site - South Brisbane
Recruitment hospital [8] 0 0
Research Site - St Albans
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2109 - Macquarie University
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment postcode(s) [6] 0 0
2800 - Orange
Recruitment postcode(s) [7] 0 0
4101 - South Brisbane
Recruitment postcode(s) [8] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
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United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
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Indiana
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United States of America
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Kansas
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United States of America
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Kentucky
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United States of America
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Louisiana
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United States of America
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Michigan
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United States of America
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Montana
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United States of America
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New York
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
Argentina
State/province [16] 0 0
Buenos Aires
Country [17] 0 0
Argentina
State/province [17] 0 0
Ciudad de Buenos Aires
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Argentina
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Rosario
Country [19] 0 0
Brazil
State/province [19] 0 0
Curitiba
Country [20] 0 0
Brazil
State/province [20] 0 0
Fortaleza
Country [21] 0 0
Brazil
State/province [21] 0 0
Porto Alegre
Country [22] 0 0
Brazil
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Ribeirão Preto
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Brazil
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Rio de Janeiro
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Brazil
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Salvador
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Brazil
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Santa Maria
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Brazil
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Sao Paulo
Country [27] 0 0
Brazil
State/province [27] 0 0
São José do Rio Preto
Country [28] 0 0
Brazil
State/province [28] 0 0
São Paulo
Country [29] 0 0
Bulgaria
State/province [29] 0 0
Pleven
Country [30] 0 0
Bulgaria
State/province [30] 0 0
Plovdiv
Country [31] 0 0
Bulgaria
State/province [31] 0 0
Sofia
Country [32] 0 0
Bulgaria
State/province [32] 0 0
Varna
Country [33] 0 0
Canada
State/province [33] 0 0
Alberta
Country [34] 0 0
Canada
State/province [34] 0 0
British Columbia
Country [35] 0 0
Canada
State/province [35] 0 0
Ontario
Country [36] 0 0
Canada
State/province [36] 0 0
Quebec
Country [37] 0 0
China
State/province [37] 0 0
Beijing
Country [38] 0 0
China
State/province [38] 0 0
Changchun
Country [39] 0 0
China
State/province [39] 0 0
Changsha
Country [40] 0 0
China
State/province [40] 0 0
Chongqing
Country [41] 0 0
China
State/province [41] 0 0
Dalian
Country [42] 0 0
China
State/province [42] 0 0
Guangzhou
Country [43] 0 0
China
State/province [43] 0 0
Hangzhou
Country [44] 0 0
China
State/province [44] 0 0
Jinan
Country [45] 0 0
China
State/province [45] 0 0
Nanchang
Country [46] 0 0
China
State/province [46] 0 0
Nanjing
Country [47] 0 0
China
State/province [47] 0 0
Shanghai
Country [48] 0 0
China
State/province [48] 0 0
Shenyang
Country [49] 0 0
China
State/province [49] 0 0
Suzhou
Country [50] 0 0
China
State/province [50] 0 0
Tianjin
Country [51] 0 0
China
State/province [51] 0 0
Urumqi
Country [52] 0 0
China
State/province [52] 0 0
Wuhan
Country [53] 0 0
China
State/province [53] 0 0
Xi'an
Country [54] 0 0
Czechia
State/province [54] 0 0
Brno
Country [55] 0 0
Czechia
State/province [55] 0 0
Hradec Kralove
Country [56] 0 0
Czechia
State/province [56] 0 0
Olomouc
Country [57] 0 0
Czechia
State/province [57] 0 0
Ostrava
Country [58] 0 0
Czechia
State/province [58] 0 0
Praha 2
Country [59] 0 0
Czechia
State/province [59] 0 0
Praha 8
Country [60] 0 0
Czechia
State/province [60] 0 0
Praha
Country [61] 0 0
Hungary
State/province [61] 0 0
Budapest
Country [62] 0 0
Hungary
State/province [62] 0 0
Debrecen
Country [63] 0 0
Hungary
State/province [63] 0 0
Gyor
Country [64] 0 0
Hungary
State/province [64] 0 0
Kecskemét
Country [65] 0 0
Hungary
State/province [65] 0 0
Szolnok
Country [66] 0 0
India
State/province [66] 0 0
Gurgaon
Country [67] 0 0
India
State/province [67] 0 0
Hubli
Country [68] 0 0
India
State/province [68] 0 0
Kolkata
Country [69] 0 0
India
State/province [69] 0 0
Mysuru
Country [70] 0 0
India
State/province [70] 0 0
Nagpur
Country [71] 0 0
India
State/province [71] 0 0
Nasik
Country [72] 0 0
India
State/province [72] 0 0
New Delhi
Country [73] 0 0
India
State/province [73] 0 0
Pune
Country [74] 0 0
Israel
State/province [74] 0 0
Haifa
Country [75] 0 0
Israel
State/province [75] 0 0
Jerusalem
Country [76] 0 0
Israel
State/province [76] 0 0
Kfar Saba
Country [77] 0 0
Israel
State/province [77] 0 0
Petach-Tikva
Country [78] 0 0
Israel
State/province [78] 0 0
Ramat Gan
Country [79] 0 0
Italy
State/province [79] 0 0
Arezzo
Country [80] 0 0
Italy
State/province [80] 0 0
Milano
Country [81] 0 0
Italy
State/province [81] 0 0
Napoli
Country [82] 0 0
Italy
State/province [82] 0 0
Orbassano
Country [83] 0 0
Italy
State/province [83] 0 0
Parma
Country [84] 0 0
Italy
State/province [84] 0 0
Pavia
Country [85] 0 0
Italy
State/province [85] 0 0
Roma
Country [86] 0 0
Italy
State/province [86] 0 0
Terni
Country [87] 0 0
Italy
State/province [87] 0 0
Verona
Country [88] 0 0
Japan
State/province [88] 0 0
Bunkyo-ku
Country [89] 0 0
Japan
State/province [89] 0 0
Chuo-ku
Country [90] 0 0
Japan
State/province [90] 0 0
Fukuoka-shi
Country [91] 0 0
Japan
State/province [91] 0 0
Hirosaki-shi
Country [92] 0 0
Japan
State/province [92] 0 0
Kanazawa-shi
Country [93] 0 0
Japan
State/province [93] 0 0
Kita-gun
Country [94] 0 0
Japan
State/province [94] 0 0
Koshigaya-shi
Country [95] 0 0
Japan
State/province [95] 0 0
Koto-ku
Country [96] 0 0
Japan
State/province [96] 0 0
Kumamoto-shi
Country [97] 0 0
Japan
State/province [97] 0 0
Kyoto-shi
Country [98] 0 0
Japan
State/province [98] 0 0
Miyazaki-city
Country [99] 0 0
Japan
State/province [99] 0 0
Nagasaki-shi
Country [100] 0 0
Japan
State/province [100] 0 0
Nagoya-shi
Country [101] 0 0
Japan
State/province [101] 0 0
Niigata-shi
Country [102] 0 0
Japan
State/province [102] 0 0
Osaka-shi
Country [103] 0 0
Japan
State/province [103] 0 0
Osakasayama-shi
Country [104] 0 0
Japan
State/province [104] 0 0
Shinjuku-ku
Country [105] 0 0
Japan
State/province [105] 0 0
Suita-shi
Country [106] 0 0
Japan
State/province [106] 0 0
Toyama-shi
Country [107] 0 0
Japan
State/province [107] 0 0
Yokohama-shi
Country [108] 0 0
Korea, Republic of
State/province [108] 0 0
Goyang-si
Country [109] 0 0
Korea, Republic of
State/province [109] 0 0
Incheon
Country [110] 0 0
Korea, Republic of
State/province [110] 0 0
Seoul
Country [111] 0 0
Korea, Republic of
State/province [111] 0 0
Suwon
Country [112] 0 0
Philippines
State/province [112] 0 0
Bacolod
Country [113] 0 0
Philippines
State/province [113] 0 0
Baguio City
Country [114] 0 0
Philippines
State/province [114] 0 0
Cebu
Country [115] 0 0
Philippines
State/province [115] 0 0
Davao City
Country [116] 0 0
Philippines
State/province [116] 0 0
Makati
Country [117] 0 0
Philippines
State/province [117] 0 0
Manila
Country [118] 0 0
Philippines
State/province [118] 0 0
Quezon City
Country [119] 0 0
Poland
State/province [119] 0 0
Bialystok
Country [120] 0 0
Poland
State/province [120] 0 0
Gdansk
Country [121] 0 0
Poland
State/province [121] 0 0
Grudziadz
Country [122] 0 0
Poland
State/province [122] 0 0
Koszalin
Country [123] 0 0
Poland
State/province [123] 0 0
Kraków
Country [124] 0 0
Poland
State/province [124] 0 0
Olsztyn
Country [125] 0 0
Poland
State/province [125] 0 0
Poznan
Country [126] 0 0
Poland
State/province [126] 0 0
Radom
Country [127] 0 0
Poland
State/province [127] 0 0
Warszawa
Country [128] 0 0
Russian Federation
State/province [128] 0 0
Ivanovo
Country [129] 0 0
Russian Federation
State/province [129] 0 0
Krasnoyarsk
Country [130] 0 0
Russian Federation
State/province [130] 0 0
Moscow
Country [131] 0 0
Russian Federation
State/province [131] 0 0
Nizhniy Novgorod
Country [132] 0 0
Russian Federation
State/province [132] 0 0
Omsk
Country [133] 0 0
Russian Federation
State/province [133] 0 0
Rostov-on-Don
Country [134] 0 0
Russian Federation
State/province [134] 0 0
Saint-Petersburg
Country [135] 0 0
Russian Federation
State/province [135] 0 0
St. Petersburg
Country [136] 0 0
Russian Federation
State/province [136] 0 0
Tyumen
Country [137] 0 0
Russian Federation
State/province [137] 0 0
Vologda
Country [138] 0 0
Spain
State/province [138] 0 0
Barcelona
Country [139] 0 0
Spain
State/province [139] 0 0
Lugo
Country [140] 0 0
Spain
State/province [140] 0 0
Madrid
Country [141] 0 0
Spain
State/province [141] 0 0
Malaga
Country [142] 0 0
Spain
State/province [142] 0 0
Santander
Country [143] 0 0
Spain
State/province [143] 0 0
Sevilla
Country [144] 0 0
Taiwan
State/province [144] 0 0
Taichung
Country [145] 0 0
Taiwan
State/province [145] 0 0
Tainan
Country [146] 0 0
Taiwan
State/province [146] 0 0
Taipei City
Country [147] 0 0
Taiwan
State/province [147] 0 0
Taipei
Country [148] 0 0
Taiwan
State/province [148] 0 0
Taoyuan
Country [149] 0 0
Thailand
State/province [149] 0 0
Bangkok
Country [150] 0 0
Thailand
State/province [150] 0 0
Khon Kaen
Country [151] 0 0
Thailand
State/province [151] 0 0
Mueang
Country [152] 0 0
Thailand
State/province [152] 0 0
Songkla
Country [153] 0 0
Turkey
State/province [153] 0 0
Adana
Country [154] 0 0
Turkey
State/province [154] 0 0
Adapazari
Country [155] 0 0
Turkey
State/province [155] 0 0
Ankara
Country [156] 0 0
Turkey
State/province [156] 0 0
Edirne
Country [157] 0 0
Turkey
State/province [157] 0 0
Istanbul
Country [158] 0 0
Turkey
State/province [158] 0 0
Izmir
Country [159] 0 0
Vietnam
State/province [159] 0 0
Ha Noi
Country [160] 0 0
Vietnam
State/province [160] 0 0
Hanoi
Country [161] 0 0
Vietnam
State/province [161] 0 0
Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.