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BRIEF TITLE: 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

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


  • Org Study ID: D419BC00001
  • Secondary ID:
  • NCT ID: NCT02516241
  • NCT Alias:
  • Sponsor: AstraZeneca - Industry
  • Source: AstraZeneca

Brief Summary

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

Detailed Description


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 Outcomes:

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

Condition:

  • Urothelial Cancer

Eligibility

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.
Show More

Gender: All

Minimum Age: 18 Years

Maximum Age: 130 Years

Healthy Volunteers: No

Overall Contact

Name: AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Locations

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