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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
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
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