Clinical trial NCT03682068: Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Unresectable Locally Advanced Urothelial Cancer
Metastatic Urothelial Cancer
Keywords: renal pelvis
ureters
urinary bladder
urethra
bladder cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-09-24
Enrollment: 1246
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: approximately 5 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: approximately 5 years
measure: Overall Survival at 24 months (OS24)
timeFrame: 24 months
measure: Progression Free Survival (PFS)
timeFrame: approximately 5 years
measure: Alive and Progression Free Survival at 12 months (APF12)
timeFrame: 12 months
measure: Objective Response Rate (ORR)
timeFrame: approximately 5 years
measure: Duration of Response (DoR)
timeFrame: approximately 5 years
measure: Disease Control Rate (DCR)
timeFrame: approximately 5 years
measure: Time from randomization to second (PFS2)
timeFrame: approximately 5 years
measure: To assess disease-related symptoms, physical functioning, and other Health-related quality of life
timeFrame: approximately 5 years
Other outcomes:
measure: To assess safety using a summary of adverse events.
timeFrame: approximately 5 years
measure: To assess pharmacokinetics of Durvalumab and Tremelimumab
timeFrame: approximately 5 years
measure: To assess immunogenicity of Durvalumab and Tremelimumab
timeFrame: approximately 5 years
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Bakersfield
country: United States
facility: Research Site
state: California
city: Fullerton
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Salinas
country: United States
facility: Research Site
state: California
city: Santa Barbara
country: United States
facility: Research Site
state: California
city: Truckee
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Fort Wayne
country: United States
facility: Research Site
state: Indiana
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: Grand Rapids
country: United States
facility: Research Site
state: Michigan
city: Bozeman
country: United States
facility: Research Site
state: Montana
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Germantown
country: United States
facility: Research Site
state: Tennessee
city: Fort Worth
country: United States
facility: Research Site
state: Texas
city: Buenos Aires
country: Argentina
facility: Research Site
city: Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aires
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: Box Hill
country: Australia
facility: Research Site
city: Elizabeth Vale
country: Australia
facility: Research Site
city: Kogarah
country: Australia
facility: Research Site
city: Macquarie University
country: Australia
facility: Research Site
city: Murdoch
country: Australia
facility: Research Site
city: Orange
country: Australia
facility: Research Site
city: South Brisbane
country: Australia
facility: Research Site
city: St Albans
country: Australia
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Fortaleza
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Ribeirão Preto
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Salvador
country: Brazil
facility: Research Site
city: Santa Maria
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São José do Rio Preto
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Dalian
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Urumqi
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Ostrava
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Praha 8
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Győr
country: Hungary
facility: Research Site
city: Kecskemét
country: Hungary
facility: Research Site
city: Szolnok
country: Hungary
facility: Research Site
city: Gurgaon
country: India
facility: Research Site
city: Hubli
country: India
facility: Research Site
city: Kolkata
country: India
facility: Research Site
city: Mysuru
country: India
facility: Research Site
city: Nagpur
country: India
facility: Research Site
city: Nasik
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Pune
country: India
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Kfar Saba
country: Israel
facility: Research Site
city: Petach-Tikva
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Arezzo
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Orbassano
country: Italy
facility: Research Site
city: Parma
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Terni
country: Italy
facility: Research Site
city: Verona
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Hirosaki-shi
country: Japan
facility: Research Site
city: Kanazawa-shi
country: Japan
facility: Research Site
city: Kita-gun
country: Japan
facility: Research Site
city: Koshigaya-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Miyazaki-city
country: Japan
facility: Research Site
city: Nagasaki-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osakasayama-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Suita-shi
country: Japan
facility: Research Site
city: Toyama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
city: Bacolod
country: Philippines
facility: Research Site
city: Baguio City
country: Philippines
facility: Research Site
city: Cebu
country: Philippines
facility: Research Site
city: Davao City
country: Philippines
facility: Research Site
city: Makati
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Grudziądz
country: Poland
facility: Research Site
city: Koszalin
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Radom
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Ivanovo
country: Russian Federation
facility: Research Site
city: Krasnoyarsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Research Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Rostov-on-Don
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Tyumen
country: Russian Federation
facility: Research Site
city: Vologda
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Lugo
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Mueang
country: Thailand
facility: Research Site
city: Songkla
country: Thailand
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Adapazari
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Ha Noi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
References: