A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination With Tremelimumab Versus Standard of Care Chemotherapy in Patients With Unresectable Stage IV Urothelial Cancer


Condition: Urothelial Cancer

Intervention:

  • Drug: MEDI4736 (Durvalumab)
  • Drug: Tremelimumab
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: Gemcitabine

Purpose: A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination with Tremelimumab Versus Standard of Care Chemotherapy in Patients with Stage IV Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02516241

Sponsor: AstraZeneca

Primary Outcome Measures:

  • Measure: To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in terms of OS in patients with unresectable Stage IV UC
  • Time Frame: Up to 4 years
  • Safety Issue:
  • Measure: To assess the efficacy of MEDI4736 monotherapy versus SoC in terms of OS in patients with unresectable Stage IV PD-L1- High UC
  • Time Frame: up to 4 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: To assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of PFS in patients with PD-L1-High UC
  • Time Frame: 4 years
  • Safety Issue:
  • Measure: To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in terms of PFS in patients with UC
  • Time Frame: 4 years
  • Safety Issue:
  • Measure: To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of ORR
  • Time Frame: 4 years
  • Safety Issue:
  • Measure: To further assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of ORR
  • Time Frame: 4 years
  • Safety Issue:
  • Measure: To assess disease-related symptoms and HRQoL in UC patients treated with MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy compared with SoC and each other using the FACT-BL questionnaire
  • Time Frame: 4 years
  • Safety Issue:
  • Measure: To assess the serum concentration of MEDI4736/tremelimumab of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy
  • Time Frame: up to 6 months
  • Safety Issue:
  • Measure: To investigate the immunogenicity of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy
  • Time Frame: 4 years
  • Safety Issue:
  • Measure: To assess the objective response rate (ORR) of MEDI4736 monotherapy in patients who are not cisplatin-eligible
  • Time Frame: 4 years
  • Safety Issue:
  • Measure: To assess the duration of response (DoR) of MEDI4736 monotherapy in patients who are not cisplatin-eligible
  • Time Frame: 4 years
  • Safety Issue:

Estimated Enrollment: 1200

Study Start Date: November 2, 2015

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum 130 Years
  • Gender: All

Inclusion Criteria:

  • Patients with histologically or cytologically documented, unresectable, Stage IV transitional cell carcinoma of the urothelium who have not been previously treated with first-line chemotherapy.
  • Patients eligible or ineligible for cisplatin-based chemotherapy. Cisplatin ineligibility is defined as meeting 1 of the following criteria: • Creatinine clearance (calculated or measured) <60 mL/min calculated by Cockcroft-Gault equation (using actual body weight) or by measured 24-hour urine collection for determination • Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 audiometric hearing loss • CTCAE Grade ≥2 peripheral neuropathy • New York Heart Association ≥Class III heart failure.
  • Tumor PD-L1 status, with Immunohistochemical (IHC) assay confirmed by a reference laboratory, must be known prior to randomization.

Exclusion Criteria:

  • Prior exposure to immune-mediated therapy, including but not limited to, other anti cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer vaccines. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
  • History of allogenic organ transplantation that requires use of immunosuppressive agents.
  • Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion: • Patients with vitiligo or alopecia • Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement • Any chronic skin condition that does not require systemic therapy • Patients without active disease in the last 3 years may be included but only after consultation with AstraZeneca • Patients with celiac disease controlled by diet alone may be included but only after consultation with AstraZeneca.
  • Brain metastases or spinal cord compression unless the patient's condition is stable and off steroids for at least 14 days prior to the start of study treatment. Patients with suspected or known brain metastases at screening should have an MRI (preferred)/CT, preferably with IV contrast to access baseline disease status.
  • Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of investigational product (IP). The following are exceptions to this criterion: • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection) • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP.

Contact:

  • AstraZeneca Clinical Study Information Center
  • 1-877-240-9479

Locations:

  • Research Site
  • Los Angeles California 90095 United States
  • Research Site
  • Stanford California 94305 United States
  • Research Site
  • Aurora Colorado 80045 United States
  • Research Site
  • New Haven Connecticut 06520 United States
  • Research Site
  • Washington District of Columbia 20007 United States
  • Research Site
  • Tampa Florida 33612 United States
  • Research Site
  • Atlanta Georgia 30322 United States
  • Research Site
  • Louisville Kentucky 40245 United States
  • Research Site
  • Boston Massachusetts 02114 United States
  • Research Site
  • Boston Massachusetts 02115 United States
  • Research Site
  • Boston Massachusetts 02215 United States
  • Research Site
  • Boston Massachusetts 02215 United States
  • Research Site
  • Ann Arbor Michigan 48109 United States
  • Research Site
  • Detroit Michigan 48201 United States
  • Research Site
  • Minneapolis Minnesota 55455 United States
  • Research Site
  • Saint Louis Missouri 63110 United States
  • Research Site
  • Omaha Nebraska 68130 United States
  • Research Site
  • Bronx New York 10467 United States
  • Research Site
  • New York New York 10021 United States
  • Research Site
  • New York New York 10029 United States
  • Research Site
  • Cleveland Ohio 44106 United States
  • Research Site
  • Memphis Tennessee 38120 United States
  • Research Site
  • Nashville Tennessee 37203 United States
  • Research Site
  • Houston Texas 77030 United States
  • Research Site
  • Seattle Washington 98101 United States
  • Research Site
  • Seattle Washington 98104 United States
  • Research Site
  • Box Hill 3128 Australia
  • Research Site
  • Elizabeth Vale 5112 Australia
  • Research Site
  • Macquarie University 2109 Australia
  • Research Site
  • St Leonards 2065 Australia
  • Research Site
  • Waratah 2298 Australia
  • Research Site
  • Linz 4010 Austria
  • Research Site
  • Wien 1020 Austria
  • Research Site
  • Wien 1090 Austria
  • Research Site
  • Wien 1140 Austria
  • Research Site
  • Brussels 1000 Belgium
  • Research Site
  • Leuven 3000 Belgium
  • Research Site
  • Liège 4000 Belgium
  • Research Site
  • Woluwé-St-Lambert 1200 Belgium
  • Research Site
  • Barretos 14784-400 Brazil
  • Research Site
  • Belo Horizonte Brazil
  • Research Site
  • Ijuí 98700-000 Brazil
  • Research Site
  • Itajai 88310-110 Brazil
  • Research Site
  • Porto Alegre 90035-003 Brazil
  • Research Site
  • Porto Alegre 90610-000 Brazil
  • Research Site
  • Porto Alegre 91350-200 Brazil
  • Research Site
  • Rio de Janeiro 20231-050 Brazil
  • Research Site
  • Rio de Janeiro 22793-080 Brazil
  • Research Site
  • Sao Paulo 01209-000 Brazil
  • Research Site
  • Sao Paulo 01321-001 Brazil
  • Research Site
  • Sao Paulo 01509-010 Brazil
  • Research Site
  • São José do Rio Preto 15090-000 Brazil
  • Research Site
  • São Paulo 01246-000 Brazil
  • Research Site
  • Calgary Alberta T2N 4N2 Canada
  • Research Site
  • Edmonton Alberta T6G 1Z2 Canada
  • Research Site
  • Kelowna British Columbia V1Y 5L3 Canada
  • Research Site
  • Vancouver British Columbia V5Z 4E6 Canada
  • Research Site
  • Halifax Nova Scotia B3H 1V7 Canada
  • Research Site
  • Hamilton Ontario L8V 5C2 Canada
  • Research Site
  • Kingston Ontario K7L 2V7 Canada
  • Research Site
  • Newmarket Ontario L3Y 2P9 Canada
  • Research Site
  • Oshawa Ontario L1G 2B9 Canada
  • Research Site
  • Ottawa Ontario K1H 1C4 Canada
  • Research Site
  • Toronto Ontario M4N 3M5 Canada
  • Research Site
  • Toronto Ontario M5G 2M9 Canada
  • Research Site
  • Sherbrooke Quebec J1H 5N4 Canada
  • Research Site
  • Quebec G1R 3S1 Canada
  • Research Site
  • Beijing 100034 China
  • Research Site
  • Beijing 100039 China
  • Research Site
  • Beijing 100191 China
  • Research Site
  • Beijing 100730 China
  • Research Site
  • Changchun 130012 China
  • Research Site
  • Changsha 410013 China
  • Research Site
  • ChongQing 400038 China
  • Research Site
  • Guangzhou 510120 China
  • Research Site
  • Hangzhou 310009 China
  • Research Site
  • Hangzhou 310014 China
  • Research Site
  • Jinan 250012 China
  • Research Site
  • Nanjing 210008 China
  • Research Site
  • Shanghai 200000 China
  • Research Site
  • Shanghai 200032 China
  • Research Site
  • Shanghai 200072 China
  • Research Site
  • Shanghai 200080 China
  • Research Site
  • Shanghai 200127 China
  • Research Site
  • Shenyang 110001 China
  • Research Site
  • Tianjin 300211 China
  • Research Site
  • Xi'an 710061 China
  • Research Site
  • Xiamen 361003 China
  • Research Site
  • Herlev 02730 Denmark
  • Research Site
  • København Ø 2100 Denmark
  • Research Site
  • Odense C 5000 Denmark
  • Research Site
  • Århus C 8000 Denmark
  • Research Site
  • Bordeaux Cedex 33075 France
  • Research Site
  • Bordeaux Cedex 33076 France
  • Research Site
  • Caen Cedex 14076 France
  • Research Site
  • Lyon Cedex 08 69373 France
  • Research Site
  • Marseille cedex 09 13273 France
  • Research Site
  • Paris Cedex 10 75475 France
  • Research Site
  • Poitiers Cedex 86021 France
  • Research Site
  • Suresnes Cedex 92151 France
  • Research Site
  • Toulouse 31059 France
  • Research Site
  • Villejuif 94805 France
  • Research Site
  • Düsseldorf 40225 Germany
  • Research Site
  • Erlangen 91054 Germany
  • Research Site
  • Hannover 30625 Germany
  • Research Site
  • Heidelberg 69120 Germany
  • Research Site
  • Jena 07747 Germany
  • Research Site
  • Lübeck 23538 Germany
  • Research Site
  • München 81675 Germany
  • Research Site
  • Münster 48149 Germany
  • Research Site
  • Athens 11528 Greece
  • Research Site
  • Heraklion 711 10 Greece
  • Research Site
  • Holargos, Athens 155 62 Greece
  • Research Site
  • Ilion Greece
  • Research Site
  • Maroussi, Athens 15125 Greece
  • Research Site
  • Patras 26500 Greece
  • Research Site
  • Thessaloniki 56 429 Greece
  • Research Site
  • Haifa 31096 Israel
  • Research Site
  • Jerusalem 91120 Israel
  • Research Site
  • Petach-Tikva 4941492 Israel
  • Research Site
  • Ramat Gan 5265601 Israel
  • Research Site
  • Zerifin 70300 Israel
  • Research Site
  • Arezzo 52100 Italy
  • Research Site
  • Genova 16100 Italy
  • Research Site
  • Meldola 47014 Italy
  • Research Site
  • Milano 20132 Italy
  • Research Site
  • Milano 20133 Italy
  • Research Site
  • Napoli 80131 Italy
  • Research Site
  • Orbassano 10043 Italy
  • Research Site
  • Pavia 27100 Italy
  • Research Site
  • Roma 00152 Italy
  • Research Site
  • San Giovanni Rotondo 71013 Italy
  • Research Site
  • Akita-shi 010-8543 Japan
  • Research Site
  • Bunkyo-ku 113-8603 Japan
  • Research Site
  • Fukuoka-shi 811-1347 Japan
  • Research Site
  • Hakata-shi 812-0033 Japan
  • Research Site
  • Hirosaki-shi 036-8563 Japan
  • Research Site
  • Hiroshima-shi 730-8518 Japan
  • Research Site
  • Izumo-shi 693-8501 Japan
  • Research Site
  • Kagoshima-shi 890-8520 Japan
  • Research Site
  • Kanazawa-shi 920-8641 Japan
  • Research Site
  • Kita-gun 761-0793 Japan
  • Research Site
  • Kobe-shi 650-0047 Japan
  • Research Site
  • Koshigaya-shi 343-8555 Japan
  • Research Site
  • Koto-ku 135-8550 Japan
  • Research Site
  • Kumamoto-shi 860-0008 Japan
  • Research Site
  • Kyoto-shi 606-8507 Japan
  • Research Site
  • Matsumoto-shi 399-8701 Japan
  • Research Site
  • Matsuyama-shi 791-0280 Japan
  • Research Site
  • Morioka-shi 020-8505 Japan
  • Research Site
  • Nagasaki-shi 852-8501 Japan
  • Research Site
  • Nagoya-shi 460-0001 Japan
  • Research Site
  • Nagoya-shi 466-8560 Japan
  • Research Site
  • Niigata-shi 951-8566 Japan
  • Research Site
  • Osaka-shi 541-8567 Japan
  • Research Site
  • Osaka-shi 545-0051 Japan
  • Research Site
  • Osakasayama-shi 589-8511 Japan
  • Research Site
  • Saga-shi 840-8571 Japan
  • Research Site
  • Sagamihara-shi 252-0315 Japan
  • Research Site
  • Sakura-shi 285-8741 Japan
  • Research Site
  • Sapporo-shi 060-8648 Japan
  • Research Site
  • Suita-shi 565-0871 Japan
  • Research Site
  • Takatsuki-shi 569-8686 Japan
  • Research Site
  • Yokohama-shi 232-0024 Japan
  • Research Site
  • Yokohama-shi 236-0004 Japan
  • Research Site
  • Incheon 21565 Korea, Republic of
  • Research Site
  • Seongnam-si 13620 Korea, Republic of
  • Research Site
  • Seoul 02841 Korea, Republic of
  • Research Site
  • Seoul 03080 Korea, Republic of
  • Research Site
  • Seoul 03722 Korea, Republic of
  • Research Site
  • Seoul 05505 Korea, Republic of
  • Research Site
  • Seoul 135-710 Korea, Republic of
  • Research Site
  • Guadalajara 44280 Mexico
  • Research Site
  • León 37000 Mexico
  • Research Site
  • Mexico, D.F 01120 Mexico
  • Research Site
  • Mexico 06760 Mexico
  • Research Site
  • Mexico 14080 Mexico
  • Research Site
  • Monterrey 64460 Mexico
  • Research Site
  • México 04739 Mexico
  • Research Site
  • Amsterdam 1066 CX Netherlands
  • Research Site
  • Amsterdam 1081 HV Netherlands
  • Research Site
  • Breda 4819 EV Netherlands
  • Research Site
  • Enschede 7512 KZ Netherlands
  • Research Site
  • Groningen 9713 GZ Netherlands
  • Research Site
  • Leiden 2333 ZA Netherlands
  • Research Site
  • Maastricht 6229 HX Netherlands
  • Research Site
  • Nijmegen 6525 GA Netherlands
  • Research Site
  • Gdańsk 80-462 Poland
  • Research Site
  • Gdańsk 80-952 Poland
  • Research Site
  • Gdynia 81-519 Poland
  • Research Site
  • Gliwice 44-101 Poland
  • Research Site
  • Katowice 40-074 Poland
  • Research Site
  • Kielce 25-734 Poland
  • Research Site
  • Olsztyn 10-228 Poland
  • Research Site
  • Otwock 05-400 Poland
  • Research Site
  • Poznan 60-780 Poland
  • Research Site
  • Szczecin 70-111 Poland
  • Research Site
  • Warszawa 02-781 Poland
  • Research Site
  • Wrocław 50-556 Poland
  • Research Site
  • Coimbra 3000-075 Portugal
  • Research Site
  • Covilhã 6200-251 Portugal
  • Research Site
  • Lisboa 1649-035 Portugal
  • Research Site
  • Lisboa 1998-018 Portugal
  • Research Site
  • Loures 2674-514 Portugal
  • Research Site
  • Porto 4099-001 Portugal
  • Research Site
  • Porto 4200-319 Portugal
  • Research Site
  • Moscow 105229 Russian Federation
  • Research Site
  • Moscow 107005 Russian Federation
  • Research Site
  • Moscow 111123 Russian Federation
  • Research Site
  • Moscow 115478 Russian Federation
  • Research Site
  • Moscow 125367 Russian Federation
  • Research Site
  • Murmansk 183047 Russian Federation
  • Research Site
  • Nizhnyi Novgorod 603001 Russian Federation
  • Research Site
  • Obninsk 249036 Russian Federation
  • Research Site
  • Obninsk 249036 Russian Federation
  • Research Site
  • Omsk 644013 Russian Federation
  • Research Site
  • Saint Petersburg 191015 Russian Federation
  • Research Site
  • Saint-Petersburg 197758 Russian Federation
  • Research Site
  • Sochi 354057 Russian Federation
  • Research Site
  • St. Petersburg 194354 Russian Federation
  • Research Site
  • St. Petersburg 199178 Russian Federation
  • Research Site
  • St.Petersburg 191014 Russian Federation
  • Research Site
  • Tjumen 625041 Russian Federation
  • Research Site
  • Ufa 450054 Russian Federation
  • Research Site
  • Yaroslavl 150054 Russian Federation
  • Research Site
  • Badajoz 06008 Spain
  • Research Site
  • Badalona 08916 Spain
  • Research Site
  • Barcelona 08003 Spain
  • Research Site
  • Barcelona 08035 Spain
  • Research Site
  • Barcelona 08243 Spain
  • Research Site
  • Elche(Alicante) 03202 Spain
  • Research Site
  • Madrid 28007 Spain
  • Research Site
  • Madrid 28040 Spain
  • Research Site
  • Madrid 28041 Spain
  • Research Site
  • Madrid 28050 Spain
  • Research Site
  • Pozuelo de Alarcon 28223 Spain
  • Research Site
  • Santiago De Compostela(A Coru 15706 Spain
  • Research Site
  • Sevilla 41013 Spain
  • Research Site
  • Valencia 46009 Spain
  • Research Site
  • Kaohsiung Taiwan
  • Research Site
  • Taichung 00407 Taiwan
  • Research Site
  • Tainan 704 Taiwan
  • Research Site
  • Taipei 100 Taiwan
  • Research Site
  • Taipei 112 Taiwan
  • Research Site
  • Taoyuan City 333 Taiwan
  • Research Site
  • Adana Turkey
  • Research Site
  • Ankara 06230 Turkey
  • Research Site
  • Ankara 6500 Turkey
  • Research Site
  • Edirne 22030 Turkey
  • Research Site
  • Istanbul 34662 Turkey
  • Research Site
  • Izmir 35100 Turkey
  • Research Site
  • Cambridge CB2 0QQ United Kingdom
  • Research Site
  • Cardiff. CF14 2TL United Kingdom
  • Research Site
  • Glasgow G12 0YN United Kingdom
  • Research Site
  • Leeds LS9 7TF United Kingdom
  • Research Site
  • London EC1A 7BE United Kingdom
  • Research Site
  • London SE1 9RT United Kingdom
  • Research Site
  • Manchester M20 4BX United Kingdom
  • Research Site
  • Sheffield S10 2SJ United Kingdom
  • Research Site
  • Southampton SO16 6YD United Kingdom
  • Research Site
  • Wirral CH63 4JY United Kingdom

View trial on ClinicalTrials.gov


E-Newsletters

Newsletter subscription

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.

Subscribe