Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer

Metastatic Urothelial Cancer Clinical Trial

— NILE  

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03682068
• Other study ID #: D933SC00001
• Secondary ID: 2018-001883-48
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 27, 2018
• Est. completion date: June 30, 2025

Study information

• Verified date: February 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1244
• Est. completion date: June 30, 2025
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Key Inclusion Criteria:

• 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 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

Related Conditions & MeSH terms

• Metastatic Urothelial Cancer
• Unresectable Locally Advanced Urothelial Cancer

Intervention

Drug:
• Durvalumab
Durvalumab IV (intravenous infusion)
• Tremelimumab
Tremelimumab IV (intravenous infusion)
• Cisplatin + Gemcitabine
Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.
• Carboplatin + Gemcitabine
Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Rosario
Australia	Research Site	Box Hill
Australia	Research Site	Elizabeth Vale
Australia	Research Site	Kogarah
Australia	Research Site	Macquarie University
Australia	Research Site	Murdoch
Australia	Research Site	Orange
Australia	Research Site	South Brisbane
Australia	Research Site	St Albans
Brazil	Research Site	Curitiba
Brazil	Research Site	Fortaleza
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Salvador
Brazil	Research Site	Santa Maria
Brazil	Research Site	São José do Rio Preto
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Varna
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chongqing
China	Research Site	Chongqing
China	Research Site	Dalian
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Jinan
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Suzhou
China	Research Site	Tianjin
China	Research Site	Tianjin
China	Research Site	Urumqi
China	Research Site	Wuhan
China	Research Site	Xi'an
Czechia	Research Site	Brno
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Olomouc
Czechia	Research Site	Ostrava
Czechia	Research Site	Praha
Czechia	Research Site	Praha 2
Czechia	Research Site	Praha 8
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Gyor
Hungary	Research Site	Kecskemét
Hungary	Research Site	Szolnok
India	Research Site	Gurgaon
India	Research Site	Hubli
India	Research Site	Kolkata
India	Research Site	Mysuru
India	Research Site	Nagpur
India	Research Site	Nasik
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	Pune
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar Saba
Israel	Research Site	Petach-Tikva
Israel	Research Site	Ramat Gan
Italy	Research Site	Arezzo
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Orbassano
Italy	Research Site	Parma
Italy	Research Site	Pavia
Italy	Research Site	Roma
Italy	Research Site	Terni
Italy	Research Site	Verona
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hirosaki-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kita-gun
Japan	Research Site	Koshigaya-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Miyazaki-city
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Suita-shi
Japan	Research Site	Toyama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Philippines	Research Site	Bacolod
Philippines	Research Site	Baguio City
Philippines	Research Site	Cebu
Philippines	Research Site	Davao City
Philippines	Research Site	Makati
Philippines	Research Site	Manila
Philippines	Research Site	Quezon City
Philippines	Research Site	Quezon City
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Grudziadz
Poland	Research Site	Koszalin
Poland	Research Site	Kraków
Poland	Research Site	Olsztyn
Poland	Research Site	Poznan
Poland	Research Site	Radom
Poland	Research Site	Warszawa
Russian Federation	Research Site	Ivanovo
Russian Federation	Research Site	Krasnoyarsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Nizhniy Novgorod
Russian Federation	Research Site	Nizhniy Novgorod
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Rostov-on-Don
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Tyumen
Russian Federation	Research Site	Vologda
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Lugo
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Santander
Spain	Research Site	Sevilla
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Mueang
Thailand	Research Site	Songkla
Turkey	Research Site	Adana
Turkey	Research Site	Adapazari
Turkey	Research Site	Ankara
Turkey	Research Site	Edirne
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
United States	Research Site	Bakersfield	California
United States	Research Site	Birmingham	Alabama
United States	Research Site	Bozeman	Montana
United States	Research Site	Chicago	Illinois
United States	Research Site	Fort Wayne	Indiana
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fullerton	California
United States	Research Site	Germantown	Tennessee
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Kansas City	Kansas
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	New Haven	Connecticut
United States	Research Site	New Hyde Park	New York
United States	Research Site	New Orleans	Louisiana
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Orlando	Florida
United States	Research Site	Rochester	New York
United States	Research Site	Salinas	California
United States	Research Site	Santa Barbara	California
United States	Research Site	Truckee	California
United States	Research Site	Washington	District of Columbia
Vietnam	Research Site	Ha Noi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  Hungary,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Philippines,  Poland,  Russian Federation,  Spain,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To assess safety using a summary of adverse events.	Adverse Events (both in terms of MedDRA preferred terms and CTCAE grade) will be listed individually by patient. The number of patients experiencing each Adverse Event will be summarized by treatment arm and CTCAE grade	approximately 5 years
Other	To assess pharmacokinetics of Durvalumab and Tremelimumab	Serum concentrations of Durvalumab and Tremelimumab	approximately 5 years
Other	To assess immunogenicity of Durvalumab and Tremelimumab	Presence of anti-drug antibodies for Durvalumab and Tremelimumab	approximately 5 years
Primary	Overall Survival (OS)	OS is defined as the time from the date of randomization until death due to any cause	approximately 5 years
Secondary	Overall Survival (OS)	Additional analysis beyond the primary endpoint	approximately 5 years
Secondary	Overall Survival at 24 months (OS24)	The OS24 will be defined as the Kaplan-Meier estimate of OS at 24 months	24 months
Secondary	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	approximately 5 years
Secondary	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	12 months
Secondary	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	approximately 5 years
Secondary	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	approximately 5 years
Secondary	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	approximately 5 years
Secondary	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	approximately 5 years
Secondary	To assess disease-related symptoms, physical functioning, and other Health-related quality of life	Collection of patient reported outcome questionnaires	approximately 5 years