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
This is a randomized, open-label, controlled, multi-center, global Phase III study to
determine the efficacy and safety of MEDI4736 (Durvalumab) monotherapy and MEDI4736
(Durvalumab) in combination with tremelimumab versus SoC (cisplatin + gemcitabine or
carboplatin + gemcitabine doublet) first-line chemotherapy in treatment-naïve patients with
histologically or cytologically documented, unresectable, Stage IV transitional cell
carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the
urothelium (including renal pelvis, ureters, urinary bladder, and urethra) and to allow
sufficient flexibility for Investigators and patients to select the agents that reflect their
normal clinical practice and national guidelines. The patients enrolled in the study will be
randomized 1:1:1 to receive treatment with combination therapy, monotherapy, or SoC
(cisplatin + gemcitabine or carboplatin + gemcitabine, based on cisplatin eligibility).
Patients will be treated with MEDI4736 (Durvalumab) or MEDI4736 (Durvalumab) with
tremelimumab, or treated with SoC until progressive disease (PD) is confirmed, unacceptable
toxicity occurs, withdrawal of consent, or another discontinuation criterion is met. Patients
will be followed for up to 2 years.
Overal Status | Start Date | Phase | Study Type |
---|---|---|---|
Recruiting | November 2, 2015 | Phase 3 | Interventional |
Primary Outcome 1 - Measure: To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in terms of OS in patients with unresectable Stage IV UC
Primary Outcome 1 - Time Frame: Up to 4 years
Primary Outcome 2 - Measure: To assess the efficacy of MEDI4736 monotherapy versus SoC in terms of OS in patients with unresectable Stage IV PD-L1- High UC
Primary Outcome 2 - Time Frame: up to 4 years
Criteria:
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.
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Gender: All
Minimum Age: 18 Years
Maximum Age: 130 Years
Healthy Volunteers: No
Name: AstraZeneca Clinical Study Information Center
Phone: 1-877-240-9479
Email: information.center@astrazeneca.com
Facility | Status | Contact |
---|---|---|
Research Site Los Angeles, California 90095 United States |
Completed | |
Research Site Stanford, California 94305 United States |
Active, not recruiting | |
Research Site Aurora, Colorado 80045 United States |
Active, not recruiting | |
Research Site New Haven, Connecticut 06520 United States |
Active, not recruiting | |
Research Site Washington, District of Columbia 20007 United States |
Withdrawn | |
Research Site Tampa, Florida 33612 United States |
Completed | |
Research Site Atlanta, Georgia 30322 United States |
Completed | |
Research Site Louisville, Kentucky 40202 United States |
Active, not recruiting | |
Research Site Boston, Massachusetts 02114 United States |
Withdrawn | |
Research Site Boston, Massachusetts 02115 United States |
Withdrawn | |
Research Site Boston, Massachusetts 02215 United States |
Active, not recruiting | |
Research Site Boston, Massachusetts 02215 United States |
Withdrawn | |
Research Site Ann Arbor, Michigan 48109 United States |
Active, not recruiting | |
Research Site Detroit, Michigan 48201 United States |
Completed | |
Research Site Minneapolis, Minnesota 55455 United States |
Withdrawn | |
Research Site Saint Louis, Missouri 63110 United States |
Withdrawn | |
Research Site Omaha, Nebraska 68130 United States |
Completed | |
Research Site Bronx, New York 10467 United States |
Withdrawn | |
Research Site New York, New York 10021 United States |
Active, not recruiting | |
Research Site New York, New York 10029 United States |
Active, not recruiting | |
Research Site Cleveland, Ohio 44106 United States |
Withdrawn | |
Research Site Memphis, Tennessee 38120 United States |
Active, not recruiting | |
Research Site Nashville, Tennessee 37203 United States |
Completed | |
Research Site Houston, Texas 77030 United States |
Withdrawn | |
Research Site Seattle, Washington 98101 United States |
Active, not recruiting | |
Research Site Seattle, Washington 98104 United States |
Withdrawn | |
Research Site Box Hill, 3128 Australia |
Active, not recruiting | |
Research Site Elizabeth Vale, 5112 Australia |
Completed | |
Research Site Macquarie University, 2109 Australia |
Active, not recruiting | |
Research Site St Leonards, 2065 Australia |
Active, not recruiting | |
Research Site Waratah, 2298 Australia |
Active, not recruiting | |
Research Site Linz, 4010 Austria |
Completed | |
Research Site Wien, 1020 Austria |
Withdrawn | |
Research Site Wien, 1090 Austria |
Completed | |
Research Site Wien, 1140 Austria |
Active, not recruiting | |
Research Site Brussels, 1000 Belgium |
Active, not recruiting | |
Research Site Bruxelles, 1200 Belgium |
Active, not recruiting | |
Research Site Leuven, 3000 Belgium |
Active, not recruiting | |
Research Site Liège, 4000 Belgium |
Active, not recruiting | |
Research Site Barretos, 14784-400 Brazil |
Active, not recruiting | |
Research Site Belo Horizonte, 30380-472 Brazil |
Active, not recruiting | |
Research Site Ijui, 98700-000 Brazil |
Completed | |
Research Site Itajai, 88310-110 Brazil |
Completed | |
Research Site Porto Alegre, 90035-003 Brazil |
Completed | |
Research Site Porto Alegre, 90610-000 Brazil |
Active, not recruiting | |
Research Site Porto Alegre, 91350-200 Brazil |
Active, not recruiting | |
Research Site Rio de Janeiro, 20231-050 Brazil |
Completed | |
Research Site Rio de Janeiro, 22793-080 Brazil |
Active, not recruiting | |
Research Site Sao Paulo, 01209-000 Brazil |
Completed | |
Research Site Sao Paulo, 01321-001 Brazil |
Completed | |
Research Site Sao Paulo, 01509-900 Brazil |
Completed | |
Research Site São José do Rio Preto, 15090-000 Brazil |
Active, not recruiting | |
Research Site São Paulo, 01246-000 Brazil |
Withdrawn | |
Research Site Calgary, Alberta T2N 4N2 Canada |
Completed | |
Research Site Edmonton, Alberta T6G 1Z2 Canada |
Completed | |
Research Site Kelowna, British Columbia V1Y 5L3 Canada |
Completed | |
Research Site Vancouver, British Columbia V5Z 4E6 Canada |
Active, not recruiting | |
Research Site Halifax, Nova Scotia B3H 1V7 Canada |
Active, not recruiting | |
Research Site Hamilton, Ontario L8V 5C2 Canada |
Active, not recruiting | |
Research Site Kingston, Ontario K7L 2V7 Canada |
Withdrawn | |
Research Site Newmarket, Ontario L3Y 2P9 Canada |
Completed | |
Research Site Oshawa, Ontario L1G 2B9 Canada |
Completed | |
Research Site Ottawa, Ontario K1H 1C4 Canada |
Completed | |
Research Site Toronto, Ontario M4N 3M5 Canada |
Active, not recruiting | |
Research Site Toronto, Ontario M5G 2M9 Canada |
Active, not recruiting | |
Research Site Sherbrooke, Quebec J1H 5N4 Canada |
Active, not recruiting | |
Research Site Quebec, G1R 3S1 Canada |
Active, not recruiting | |
Research Site Beijing, 100034 China |
Recruiting | |
Research Site Beijing, 100039 China |
Recruiting | |
Research Site Beijing, 100191 China |
Recruiting | |
Research Site Beijing, 100730 China |
Not yet recruiting | |
Research Site Changchun, 130012 China |
Recruiting | |
Research Site Changsha, 410013 China |
Recruiting | |
Research Site ChongQing, 400038 China |
Recruiting | |
Research Site Guangzhou, 510120 China |
Withdrawn | |
Research Site Hangzhou, 310009 China |
Recruiting | |
Research Site Hangzhou, 310014 China |
Recruiting | |
Research Site Jinan, 250012 China |
Not yet recruiting | |
Research Site Nanjing, 210008 China |
Recruiting | |
Research Site Shanghai, 200000 China |
Recruiting | |
Research Site Shanghai, 200032 China |
Recruiting | |
Research Site Shanghai, 200072 China |
Recruiting | |
Research Site Shanghai, 200080 China |
Recruiting | |
Research Site Shanghai, 200127 China |
Recruiting | |
Research Site Shenyang, 110001 China |
Recruiting | |
Research Site Tianjin, 300211 China |
Recruiting | |
Research Site Xi'an, 710061 China |
Recruiting | |
Research Site Xiamen, 361003 China |
Recruiting | |
Research Site Herlev, 2730 Denmark |
Completed | |
Research Site København Ø, 2100 Denmark |
Completed | |
Research Site Odense C, 5000 Denmark |
Completed | |
Research Site Århus C, 8000 Denmark |
Completed | |
Research Site Bordeaux Cedex, 33075 France |
Active, not recruiting | |
Research Site Bordeaux, 33000 France |
Active, not recruiting | |
Research Site Caen Cedex, 14076 France |
Active, not recruiting | |
Research Site Lyon Cedex 08, 69373 France |
Active, not recruiting | |
Research Site Marseille cedex 09, 13273 France |
Completed | |
Research Site Paris Cedex 10, 75475 France |
Completed | |
Research Site Poitiers Cedex, 86021 France |
Completed | |
Research Site Suresnes Cedex, 92151 France |
Active, not recruiting | |
Research Site Toulouse, 31059 France |
Active, not recruiting | |
Research Site Villejuif, 94805 France |
Active, not recruiting | |
Research Site Düsseldorf, 40225 Germany |
Completed | |
Research Site Erlangen, 91054 Germany |
Completed | |
Research Site Hannover, 30625 Germany |
Completed | |
Research Site Heidelberg, 69120 Germany |
Completed | |
Research Site Jena, 07747 Germany |
Completed | |
Research Site Lübeck, 23538 Germany |
Withdrawn | |
Research Site München, 81675 Germany |
Active, not recruiting | |
Research Site Münster, 48149 Germany |
Active, not recruiting | |
Research Site Athens, 11528 Greece |
Active, not recruiting | |
Research Site Heraklion, 711 11 Greece |
Active, not recruiting | |
Research Site Holargos, Athens, 155 62 Greece |
Active, not recruiting | |
Research Site Ilion, Greece |
Active, not recruiting | |
Research Site Maroussi, Athens, 15125 Greece |
Active, not recruiting | |
Research Site Patras, 26500 Greece |
Active, not recruiting | |
Research Site Thessaloniki, 56 429 Greece |
Completed | |
Research Site Haifa, 31096 Israel |
Active, not recruiting | |
Research Site Jerusalem, 91120 Israel |
Completed | |
Research Site Petach-Tikva, 4941492 Israel |
Active, not recruiting | |
Research Site Ramat Gan, 5265601 Israel |
Active, not recruiting | |
Research Site Zerifin, 70300 Israel |
Completed | |
Research Site Arezzo, 52100 Italy |
Active, not recruiting | |
Research Site Genova, 16100 Italy |
Withdrawn | |
Research Site Meldola, 47014 Italy |
Active, not recruiting | |
Research Site Milano, 20132 Italy |
Active, not recruiting | |
Research Site Milano, 20133 Italy |
Active, not recruiting | |
Research Site Napoli, 80131 Italy |
Completed | |
Research Site Orbassano, 10043 Italy |
Active, not recruiting | |
Research Site Pavia, 27100 Italy |
Completed | |
Research Site Roma, 00152 Italy |
Completed | |
Research Site San Giovanni Rotondo, 71013 Italy |
Active, not recruiting | |
Research Site Akita-shi, 010-8543 Japan |
Active, not recruiting | |
Research Site Bunkyo-ku, 113-8603 Japan |
Completed | |
Research Site Fukuoka-shi, 811-1347 Japan |
Active, not recruiting | |
Research Site Hakata-shi, 812-0033 Japan |
Completed | |
Research Site Hirosaki-shi, 036-8563 Japan |
Active, not recruiting | |
Research Site Hiroshima-shi, 730-8518 Japan |
Active, not recruiting | |
Research Site Izumo-shi, 693-8501 Japan |
Completed | |
Research Site Kagoshima-shi, 890-8520 Japan |
Completed | |
Research Site Kanazawa-shi, 920-8641 Japan |
Active, not recruiting | |
Research Site Kita-gun, 761-0793 Japan |
Active, not recruiting | |
Research Site Kobe-shi, 650-0047 Japan |
Completed | |
Research Site Koshigaya-shi, 343-8555 Japan |
Completed | |
Research Site Koto-ku, 135-8550 Japan |
Completed | |
Research Site Kumamoto-shi, 860-0008 Japan |
Active, not recruiting | |
Research Site Kyoto-shi, 606-8507 Japan |
Active, not recruiting | |
Research Site Matsumoto-shi, 399-8701 Japan |
Withdrawn | |
Research Site Matsuyama-shi, 791-0280 Japan |
Active, not recruiting | |
Research Site Morioka-shi, 020-8505 Japan |
Completed | |
Research Site Nagasaki-shi, 852-8501 Japan |
Active, not recruiting | |
Research Site Nagoya-shi, 460-0001 Japan |
Completed | |
Research Site Nagoya-shi, 466-8560 Japan |
Active, not recruiting | |
Research Site Niigata-shi, 951-8566 Japan |
Withdrawn | |
Research Site Osaka-shi, 541-8567 Japan |
Completed | |
Research Site Osaka-shi, 545-8586 Japan |
Completed | |
Research Site Osakasayama-shi, 589-8511 Japan |
Active, not recruiting | |
Research Site Saga-shi, 840-8571 Japan |
Active, not recruiting | |
Research Site Sagamihara-shi, 252-0315 Japan |
Completed | |
Research Site Sakura-shi, 285-8741 Japan |
Completed | |
Research Site Sapporo-shi, 060-8648 Japan |
Completed | |
Research Site Suita-shi, 565-0871 Japan |
Active, not recruiting | |
Research Site Takatsuki-shi, 569-8686 Japan |
Completed | |
Research Site Yokohama-shi, 232-0024 Japan |
Completed | |
Research Site Yokohama-shi, 236-0004 Japan |
Completed | |
Research Site Incheon, 21565 Korea, Republic of |
Active, not recruiting | |
Research Site Seongnam-si, 13620 Korea, Republic of |
Active, not recruiting | |
Research Site Seoul, 02841 Korea, Republic of |
Completed | |
Research Site Seoul, 03080 Korea, Republic of |
Active, not recruiting | |
Research Site Seoul, 03722 Korea, Republic of |
Active, not recruiting | |
Research Site Seoul, 05505 Korea, Republic of |
Active, not recruiting | |
Research Site Seoul, 135-710 Korea, Republic of |
Active, not recruiting | |
Research Site Guadalajara, 44280 Mexico |
Active, not recruiting | |
Research Site León, 37000 Mexico |
Completed | |
Research Site Mexico, D.F, 01120 Mexico |
Completed | |
Research Site Mexico, 06760 Mexico |
Completed | |
Research Site Mexico, 14080 Mexico |
Withdrawn | |
Research Site Monterrey, 64460 Mexico |
Completed | |
Research Site México, 04739 Mexico |
Completed | |
Research Site Amsterdam, 1066 CX Netherlands |
Active, not recruiting | |
Research Site Amsterdam, 1081 HV Netherlands |
Active, not recruiting | |
Research Site Breda, 4819 EV Netherlands |
Active, not recruiting | |
Research Site Enschede, 7512 KZ Netherlands |
Completed | |
Research Site Groningen, 9713 GZ Netherlands |
Active, not recruiting | |
Research Site Leiden, 2333 ZA Netherlands |
Completed | |
Research Site Maastricht, 6229 HX Netherlands |
Active, not recruiting | |
Research Site Nijmegen, 6525 GA Netherlands |
Active, not recruiting | |
Research Site Gdańsk, 80-214 Poland |
Completed | |
Research Site Gdańsk, 80-462 Poland |
Terminated | |
Research Site Gdynia, 81-519 Poland |
Completed | |
Research Site Gliwice, 44-101 Poland |
Completed | |
Research Site Katowice, 40-074 Poland |
Withdrawn | |
Research Site Kielce, 25-734 Poland |
Withdrawn | |
Research Site Olsztyn, 10-228 Poland |
Completed | |
Research Site Otwock, 05-400 Poland |
Active, not recruiting | |
Research Site Poznan, 60-780 Poland |
Withdrawn | |
Research Site Szczecin, 70-111 Poland |
Completed | |
Research Site Warszawa, 02-781 Poland |
Completed | |
Research Site Wrocław, 50-556 Poland |
Withdrawn | |
Research Site Coimbra, 3000-075 Portugal |
Withdrawn | |
Research Site Covilhã, 6200-251 Portugal |
Withdrawn | |
Research Site Lisboa, 1649-035 Portugal |
Active, not recruiting | |
Research Site Lisboa, 1998-018 Portugal |
Withdrawn | |
Research Site Loures, 2674-514 Portugal |
Completed | |
Research Site Porto, 4099-001 Portugal |
Active, not recruiting | |
Research Site Porto, 4200-319 Portugal |
Withdrawn | |
Research Site Moscow, 105229 Russian Federation |
Active, not recruiting | |
Research Site Moscow, 107005 Russian Federation |
Withdrawn | |
Research Site Moscow, 111123 Russian Federation |
Withdrawn | |
Research Site Moscow, 115478 Russian Federation |
Active, not recruiting | |
Research Site Moscow, 125367 Russian Federation |
Withdrawn | |
Research Site Murmansk, 183047 Russian Federation |
Completed | |
Research Site Nizhnyi Novgorod, 603001 Russian Federation |
Active, not recruiting | |
Research Site Obninsk, 249036 Russian Federation |
Active, not recruiting | |
Research Site Obninsk, 249036 Russian Federation |
Completed | |
Research Site Omsk, 644013 Russian Federation |
Active, not recruiting | |
Research Site Saint Petersburg, 191015 Russian Federation |
Active, not recruiting | |
Research Site Saint-Petersburg, 197758 Russian Federation |
Active, not recruiting | |
Research Site Sochi, 354057 Russian Federation |
Withdrawn | |
Research Site St. Petersburg, 194354 Russian Federation |
Active, not recruiting | |
Research Site St. Petersburg, 199178 Russian Federation |
Active, not recruiting | |
Research Site St.Petersburg, 191014 Russian Federation |
Completed | |
Research Site Tjumen, 625041 Russian Federation |
Withdrawn | |
Research Site Ufa, 450054 Russian Federation |
Active, not recruiting | |
Research Site Yaroslavl, 150054 Russian Federation |
Completed | |
Research Site Badajoz, 06008 Spain |
Active, not recruiting | |
Research Site Badalona, 08916 Spain |
Active, not recruiting | |
Research Site Barcelona, 08003 Spain |
Active, not recruiting | |
Research Site Barcelona, 08035 Spain |
Active, not recruiting | |
Research Site Barcelona, 08243 Spain |
Active, not recruiting | |
Research Site Elche(Alicante), 03202 Spain |
Active, not recruiting | |
Research Site Madrid, 28007 Spain |
Active, not recruiting | |
Research Site Madrid, 28040 Spain |
Active, not recruiting | |
Research Site Madrid, 28041 Spain |
Active, not recruiting | |
Research Site Madrid, 28050 Spain |
Active, not recruiting | |
Research Site Pozuelo de Alarcon, 28223 Spain |
Completed | |
Research Site Santiago de Compostela, 15706 Spain |
Active, not recruiting | |
Research Site Sevilla, 41013 Spain |
Active, not recruiting | |
Research Site Valencia, 46009 Spain |
Withdrawn | |
Research Site Kaohsiung, Taiwan |
Active, not recruiting | |
Research Site Taichung, 00407 Taiwan |
Active, not recruiting | |
Research Site Tainan, 704 Taiwan |
Active, not recruiting | |
Research Site Taipei, 10002 Taiwan |
Completed | |
Research Site Taipei, 112 Taiwan |
Active, not recruiting | |
Research Site Taoyuan City, 333 Taiwan |
Active, not recruiting | |
Research Site Adana, Turkey |
Withdrawn | |
Research Site Ankara, 06230 Turkey |
Completed | |
Research Site Ankara, 6500 Turkey |
Withdrawn | |
Research Site Edirne, 22030 Turkey |
Completed | |
Research Site Istanbul, 34662 Turkey |
Withdrawn | |
Research Site Izmir, 35100 Turkey |
Completed | |
Research Site Cambridge, CB2 0QQ United Kingdom |
Completed | |
Research Site Cardiff., CF14 2TL United Kingdom |
Active, not recruiting | |
Research Site Glasgow, G12 0YN United Kingdom |
Active, not recruiting | |
Research Site Leeds, LS9 7TF United Kingdom |
Active, not recruiting | |
Research Site London, EC1A 7BE United Kingdom |
Active, not recruiting | |
Research Site London, SE1 9RT United Kingdom |
Completed | |
Research Site Manchester, M20 4BX United Kingdom |
Active, not recruiting | |
Research Site Sheffield, S10 2SJ United Kingdom |
Active, not recruiting | |
Research Site Southampton, SO16 6YD United Kingdom |
Active, not recruiting | |
Research Site Wirral, CH63 4JY United Kingdom |
Completed |