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Assessment of Efficacy and Safety of Durvalumab Plus BCG Compared to the Standard Therapy With BCG in Non-muscle Invasive Bladder Cancer (POTOMAC)

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ClinicalTrials.gov Identifier: NCT03528694
Recruitment Status : Recruiting
First Posted : May 18, 2018
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a randomized, open-label, multi-center, global, phase III study to determine the efficacy and safety of Durvalumab + BCG combination therapy in the treatment of patients with non-muscle-invasive bladder cancer.

Condition or disease Intervention/treatment Phase
Non-muscle-invasive Bladder Cancer Biological: Durvalumab (MEDI4736) Biological: Bacillus Calmette-Guerin (BCG) Phase 3

Detailed Description:
Patients will be randomized in a 1:1:1 ratio to receive treatment with Durvalumab + BCG combination therapies, or Standard of Care (SoC) therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 975 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Open-Label, Multi-Center, Global Study of Durvalumab and Bacillus Calmette-Guerin (BCG) Administered as Combination Therapy Versus BCG Alone in High-Risk, BCG Naïve Non-Muscle Invasive Bladder Cancer Patients
Actual Study Start Date : May 14, 2018
Estimated Primary Completion Date : November 24, 2021
Estimated Study Completion Date : November 25, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Experimental: Durvalumab plus BCG (induction + maintenance)
Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy
Biological: Durvalumab (MEDI4736)
Investigational product

Biological: Bacillus Calmette-Guerin (BCG)
Standard of care

Experimental: Durvalumab plus BCG (induction only)
Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy
Biological: Durvalumab (MEDI4736)
Investigational product

Biological: Bacillus Calmette-Guerin (BCG)
Standard of care

Active Comparator: BCG treatment (Standard of care therapy)
Bacillus Calmette-Guerrin (BCG) standard of care treatment
Biological: Bacillus Calmette-Guerin (BCG)
Standard of care




Primary Outcome Measures :
  1. The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of Disease free survival (DFS) in patients with NMIBC [ Time Frame: Up to 4 years ]

Secondary Outcome Measures :
  1. The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of DFS after 24 months of last subject's last dose of IP [ Time Frame: Up to 4 years ]
  2. Disease-related symptoms and HRQoL in patients with NMIBC treated with Durvalumab + BCG combination therapies compared to SoC and compared to each other using the EORTC QLQ-C30 questionnaire [ Time Frame: Up to 4 years ]
    EORTC QLQ-C30 measures cancer patients' functioning (HRQoL) and symptoms for all cancer types and consists of functional, symptom and a global measure of health status scales

  3. Patient-reported treatment tolerability using specific PRO CTCAE symptoms [ Time Frame: Up to 4 years ]
  4. The serum concentration of Durvalumab plus BCG combination therapies [ Time Frame: Up to 4 years ]
  5. The immunogenicity of Durvalumab when used in combination with BCG treatment assessed by descriptive summary of presence of ADAs [ Time Frame: Up to 4 years ]
    Serum will be tested for the presence of anti-drug antibodies.

  6. The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of OS [ Time Frame: Up to 7 years ]
  7. The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of time to muscle invasive bladder cancer and/or metastatic disease [ Time Frame: Up to 7 years ]
  8. The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of DFS after 24 months of last subject's last dose of IP [ Time Frame: Up to 4 years ]
  9. The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of DFS after 24 months of last subject's last dose of IP [ Time Frame: Up to 4 years ]
  10. The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of OS [ Time Frame: Up to 7 years ]
  11. The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of OS [ Time Frame: Up to 7 years ]
  12. The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of time to muscle invasive bladder cancer and/or metastatic disease [ Time Frame: Up to 7 years ]
  13. The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of time to muscle invasive bladder cancer and/or metastatic disease [ Time Frame: Up to 7 years ]
  14. Disease-related symptoms and HRQoL in patients with NMIBC treated with Durvalumab + BCG combination therapies compared to SoC and compared to each other using the the EORTC QLQ NMIBC24 questionnaire [ Time Frame: Up to 4 years ]
    EORTC QLQ-NMIBC24 assesses disease-specific symptoms of patients with intermediate to high-risk NMIBC.


Other Outcome Measures:
  1. Number of treatment-related adverse events as assessed by CTCAE v4.0 in patients receiving Durvalumab + BCG combination therapies compared to SoC [ Time Frame: Up to 4 years ]
    The safety and tolerability profile of Durvalumab + BCG combination therapies compared to SoC using vital signs, laboratory data, electrocardiograms (ECGs), and adverse event data.



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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: For inclusion in the study, patients should fulfill the following criteria:

  • Aged at least 18 years
  • BCG-naïve (patients who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before study entry are eligible)
  • Local histological confirmation (based on pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. A high risk tumor is defined as one of the following

    • T1 tumor
    • High grade/ G3 tumor
    • CIS
    • Multiple and recurrent and large (with diameter of largest tumor ≥3 cm) tumors (all conditions must be met in this point)
  • Complete resection of all Ta/T1 papillary disease prior to randomization, with the TURBT removing high-risk NMIBC performed not more than 4 months before randomization in the study. Patients with residual CIS after TURBT are eligible
  • No prior radiotherapy for bladder cancer
  • No prior exposure to immune-mediated therapy of cancer including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 antibodies. Patients who have been treated with anticancer vaccines will be excluded

Exclusion Criteria:

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

  • Evidence of muscle-invasive, locally advanced, metastatic, and/or extra vesical bladder cancer (ie, T2, T3, T4, and / or stage IV)
  • Concurrent extravesical (ie, urethra, ureter, or renal pelvis), non-muscle-invasive transitional cell carcinoma of the urothelium
  • Previous investigational product (IP) assignment in the present study
  • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer related conditions (eg, hormone replacement therapy) is acceptable. Chemotherapy for previous instances of NMIBC is acceptable.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:

    • Patients with vitiligo or alopecia
    • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
    • Any chronic skin condition that does not require systemic therapy
    • Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
    • Patients with celiac disease controlled by diet alone
  • History of another primary malignancy except for

    - Malignancy treated with curative intent and with no known active disease ≥ 2 years before the first dose of IP and of low potential risk for recurrence during the study period

    • Adequately treated nonmelanoma skin cancer or lentigo maligna withoutevidence of disease
    • Adequately treated CIS without evidence of disease
    • Prostate cancer (tumor/node/metastasis stage) of stage ≤ T2cN0M0 without biochemical recurrence or progression that in the opinion of the Investigator does not require active intervention
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. 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, computed tomography [CT] scan premedication)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03528694


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

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Locations
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Australia
Research Site Recruiting
Auchenflower, Australia, 4066
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Box Hill, Australia, 3128
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Brisbane, Australia, 4122
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Kogarah, Australia, 2217
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Orange, Australia, 2800
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Parkville, Australia, 3000
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Westmead, Australia, 2145
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Wollongong, Australia, 2500
Austria
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Innsbruck, Austria, 6020
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Linz, Austria, 4020
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Wien, Austria, 1090
Belgium
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Brussels, Belgium, 1070
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Gent, Belgium, 9000
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Leuven, Belgium, 3000
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Roeselare, Belgium, 8800
Canada, British Columbia
Research Site Withdrawn
Burnaby, British Columbia, Canada, V5G 2X6
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Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Nova Scotia
Research Site Withdrawn
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
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Hamilton, Ontario, Canada, L8V 5C2
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Kingston, Ontario, Canada, K7L 3J7
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Ottawa, Ontario, Canada, K1H 8L6
Research Site Withdrawn
Toronto, Ontario, Canada, M4N 3M5
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Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
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Chicoutimi, Quebec, Canada, G7H 5H6
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Montreal, Quebec, Canada, H2X 3E4
Canada
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Quebec, Canada, G1R 3S1
France
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Amiens, France, 80480
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Angers Cedex 01, France, 49033
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Bordeaux Cedex, France, 33076
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LYON cedex 03, France, 69437
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Marseille, France, 13003
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Montpellier CEDEX 5, France, 34295
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Strasbourg Cedex, France, 67091
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Suresnes, France, 92151
Germany
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Berlin, Germany, 12200
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Duisburg, Germany, 47179
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Hamburg, Germany, 22399
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Hannover, Germany, 30625
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Heidelberg, Germany, 69120
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Heinsberg, Germany, 52525
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Köln, Germany, 50968
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Marburg, Germany, 35043
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Mettmann, Germany, 40822
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Mühlheim An Der Ruhr, Germany, 45468
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München, Germany, 81377
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Münster, Germany, 48149
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Nürtingen, Germany, 72766
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Wesel, Germany
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Würselen, Germany, 52146
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Zirndorf, Germany, 90513
Japan
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Bunkyo-ku, Japan, 113-8603
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Fukuoka, Japan, 812-8582
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Kanazawa-shi, Japan, 920-8641
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Kita-gun, Japan, 761-0793
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Koto-ku, Japan, 135-8550
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Matsuyama-shi, Japan, 791-0280
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Miyazaki-city, Japan, 889-1692
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Nagasaki-shi, Japan, 852-8501
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Nagoya-shi, Japan, 467-0001
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Okayama-shi, Japan, 700-8558
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Osaka-shi, Japan, 541-8567
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Osakasayama-shi, Japan, 589-8511
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Sapporo-shi, Japan, 060-8543
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Shinjuku-ku, Japan, 160-8582
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Toyama-shi, Japan, 930-0194
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Tsukuba-shi, Japan, 305-8576
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Yokohama-shi, Japan, 232-0024
Netherlands
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Arnhem, Netherlands, 6815 AD
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Brussels, Netherlands, 1090
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Leiden, Netherlands, 2333 ZA
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Leuven, Netherlands, 3000
Poland
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Białystok, Poland, 15-950
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Bydgoszcz, Poland, 85-681
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Gdańsk, Poland, 80-214
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Koszalin, Poland, 75-581
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Olsztyn, Poland, 10-513
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Piotrków Trybunalski, Poland, 97-300
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Poznań, Poland, 60-848
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Warszawa, Poland, 02-005
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Warszawa, Poland, 02-781
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Wroclaw, Poland, 53-413
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Wrocław, Poland, 50-556
Russian Federation
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Ivanovo, Russian Federation, 153040
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Krasnoyarsk, Russian Federation, 660133
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Moscow, Russian Federation, 115280
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Nizhniy Novgorod, Russian Federation, 603074
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Obninsk, Russian Federation, 249036
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Omsk, Russian Federation, 644013
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Saint Petersburg, Russian Federation, 195271
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St Petersburg, Russian Federation, 194044
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St. Petersburg, Russian Federation, 194017
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St. Petersburg, Russian Federation, 197758
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St.Petersburg, Russian Federation, 191014
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Vladimir, Russian Federation, 600020
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Vologda, Russian Federation, 160012
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Yaroslavl, Russian Federation, 150054
Slovakia
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Banka, Slovakia, 921 01
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Bratislava, Slovakia, 811 08
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Bratislava, Slovakia, 812 50
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Martin, Slovakia, 036 59
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Presov, Slovakia, 08001
Spain
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Badajoz, Spain, 06008
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Barcelona, Spain, 08035
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Barcelona, Spain, 08036
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Barcelona, Spain, 08208
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Elche(Alicante), Spain, 03202
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Madrid, Spain, 28040
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Madrid, Spain, 28041
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Madrid, Spain, 28046
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Malaga, Spain, 29010
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Oviedo, Spain, 33011
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Pamplona, Spain, 31008
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Pozuelo de Alarcon, Spain, 28223
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Sevilla, Spain, 41009
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Sevilla, Spain, 41014
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Valencia, Spain, 46014
United Kingdom
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Birmingham, United Kingdom, B15 2TH
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Cleveland, United Kingdom, TS4 3BW
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Glasgow, United Kingdom, G12 0YN
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Guildford, United Kingdom, CU2 7XX
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London, United Kingdom, EC1A 7BE
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London, United Kingdom, NW1 2PG
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London, United Kingdom, SE1 9RY
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Sheffield, United Kingdom, S10 2RX
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Southampton, United Kingdom, SO16 6YD
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Taunton, United Kingdom, TA1 5DA
Sponsors and Collaborators
AstraZeneca

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03528694     History of Changes
Other Study ID Numbers: D419JC00001
First Posted: May 18, 2018    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by AstraZeneca:
Durvalumab
BCG
MEDI4736
NMIBC
PD-L1
DFS
OS
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Durvalumab
Antibodies, Monoclonal
BCG Vaccine
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic