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
Condition: Non-muscle-invasive Bladder Cancer
Intervention:
- Biological: Durvalumab (MEDI4736)
- Biological: Bacillus Calmette-Guerin (BCG)
Purpose: 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.
Study Type: Interventional
Clinical Trials Identifier NCT 8-digits: NCT03528694
Sponsor: AstraZeneca
Primary Outcome Measures:
- Measure: 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
- Safety Issue:
Secondary Outcome Measures:
- Measure: 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
- Safety Issue:
- Measure: 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
- Safety Issue:
- Measure: Patient-reported treatment tolerability using specific PRO CTCAE symptoms
- Time Frame: Up to 4 years
- Safety Issue:
- Measure: The serum concentration of Durvalumab plus BCG combination therapies
- Time Frame: Up to 4 years
- Safety Issue:
- Measure: 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
- Safety Issue:
- Measure: The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of OS
- Time Frame: Up to 7 years
- Safety Issue:
- Measure: 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
- Safety Issue:
- Measure: 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
- Safety Issue:
- Measure: 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
- Safety Issue:
- Measure: The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of OS
- Time Frame: Up to 7 years
- Safety Issue:
- Measure: The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of OS
- Time Frame: Up to 7 years
- Safety Issue:
- Measure: 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
- Safety Issue:
- Measure: 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
- Safety Issue:
- Measure: 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
- Safety Issue:
Estimated Enrollment: 975
Study Start Date: May 14, 2018
Phase: Phase 3
Eligibility:
- Age: minimum 18 Years maximum 130 Years
- Gender: All
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:
- 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)
Contact:
- AstraZeneca Clinical Study Information Center
- 1-877-240-9479
Locations:
- Research Site
- Auchenflower 4066 Australia
- Research Site
- Box Hill 3128 Australia
- Research Site
- Brisbane 4122 Australia
- Research Site
- Kogarah 2217 Australia
- Research Site
- Orange 2800 Australia
- Research Site
- Parkville 3000 Australia
- Research Site
- Westmead 2145 Australia
- Research Site
- Innsbruck 6020 Austria
- Research Site
- Linz 4020 Austria
- Research Site
- Wien 1090 Austria
- Research Site
- Brussels 1070 Belgium
- Research Site
- Gent 9000 Belgium
- Research Site
- Leuven 3000 Belgium
- Research Site
- Roeselare 8800 Belgium
- Research Site
- Burnaby British Columbia V5G 2X6 Canada
- Research Site
- Vancouver British Columbia V5Z 1M9 Canada
- Research Site
- Halifax Nova Scotia B3H 2Y9 Canada
- Research Site
- Hamilton Ontario L8V 5C2 Canada
- Research Site
- Kingston Ontario K7L 3J7 Canada
- Research Site
- Ottawa Ontario K1H 8L6 Canada
- Research Site
- Toronto Ontario M4N 3M5 Canada
- Research Site
- Toronto Ontario M5G 2M9 Canada
- Research Site
- Chicoutimi Quebec G7H 5H6 Canada
- Research Site
- Montreal Quebec H2X 3E4 Canada
- Research Site
- Quebec G1R 3S1 Canada
- Research Site
- Amiens Cedex 1 80054 France
- Research Site
- Angers Cedex 01 49033 France
- Research Site
- Bordeaux Cedex 33076 France
- Research Site
- LYON cedex 03 69437 France
- Research Site
- Marseille 13003 France
- Research Site
- Montpellier CEDEX 5 34295 France
- Research Site
- Strasbourg Cedex 67091 France
- Research Site
- Suresnes 92151 France
- Research Site
- Berlin 12200 Germany
- Research Site
- Duisburg 47179 Germany
- Research Site
- Hamburg 22399 Germany
- Research Site
- Hannover 30625 Germany
- Research Site
- Heidelberg 69120 Germany
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- Köln 50968 Germany
- Research Site
- Marburg 35043 Germany
- Research Site
- Mettmann 40822 Germany
- Research Site
- Mühlheim An Der Ruhr 45468 Germany
- Research Site
- München 81377 Germany
- Research Site
- Münster 48149 Germany
- Research Site
- Nürtingen 72766 Germany
- Research Site
- Zirndorf 90513 Germany
- Research Site
- Bunkyo-ku 113-8603 Japan
- Research Site
- Fukuoka 812-8582 Japan
- Research Site
- Kanazawa-shi 920-8641 Japan
- Research Site
- Kita-gun 761-0793 Japan
- Research Site
- Koto-ku 135-8550 Japan
- Research Site
- Matsuyama-shi 791-0280 Japan
- Research Site
- Miyazaki-city 889-1692 Japan
- Research Site
- Nagasaki-shi 852-8501 Japan
- Research Site
- Nagoya-shi 467-0001 Japan
- Research Site
- Okayama-shi 700-8558 Japan
- Research Site
- Osaka-shi 541-8567 Japan
- Research Site
- Osakasayama-shi 589-8511 Japan
- Research Site
- Sapporo-shi 060-8543 Japan
- Research Site
- Shinjuku-ku 160-8582 Japan
- Research Site
- Toyama-shi 930-0194 Japan
- Research Site
- Tsukuba-shi 305-8576 Japan
- Research Site
- Yokohama-shi 232-0024 Japan
- Research Site
- Arnhem 6815 AD Netherlands
- Research Site
- Brussels 1090 Netherlands
- Research Site
- Leiden 2333 ZA Netherlands
- Research Site
- Leuven 3000 Netherlands
- Research Site
- Białystok 15-950 Poland
- Research Site
- Bydgoszcz 85-681 Poland
- Research Site
- Gdańsk 80-952 Poland
- Research Site
- Koszalin 75-581 Poland
- Research Site
- Olsztyn 10-513 Poland
- Research Site
- Piotrków Trybunalski 97-300 Poland
- Research Site
- Poznań 60-848 Poland
- Research Site
- Warszawa 02-005 Poland
- Research Site
- Warszawa 02-781 Poland
- Research Site
- Wroclaw 53-413 Poland
- Research Site
- Wrocław 50-556 Poland
- Research Site
- Ivanovo 153040 Russian Federation
- Research Site
- Krasnoyarsk 660133 Russian Federation
- Research Site
- Moscow 115280 Russian Federation
- Research Site
- Nizhniy Novgorod 603074 Russian Federation
- Research Site
- Obninsk 249036 Russian Federation
- Research Site
- Omsk 644013 Russian Federation
- Research Site
- Saint Petersburg 195271 Russian Federation
- Research Site
- St. Petersburg 194017 Russian Federation
- Research Site
- St. Petersburg 197758 Russian Federation
- Research Site
- Vladimir 600020 Russian Federation
- Research Site
- Vologda 160012 Russian Federation
- Research Site
- Yaroslavl 150054 Russian Federation
- Research Site
- Banka 921 01 Slovakia
- Research Site
- Bratislava 811 08 Slovakia
- Research Site
- Bratislava 812 50 Slovakia
- Research Site
- Martin 036 59 Slovakia
- Research Site
- Presov 08001 Slovakia
- Research Site
- Badajoz 06008 Spain
- Research Site
- Barcelona 08035 Spain
- Research Site
- Barcelona 08036 Spain
- Research Site
- Barcelona 08208 Spain
- Research Site
- Elche(Alicante) 03202 Spain
- Research Site
- Madrid 28040 Spain
- Research Site
- Madrid 28041 Spain
- Research Site
- Madrid 28046 Spain
- Research Site
- Malaga 29010 Spain
- Research Site
- Oviedo 33011 Spain
- Research Site
- Pamplona 31008 Spain
- Research Site
- Pozuelo de Alarcon 28223 Spain
- Research Site
- Sevilla 41009 Spain
- Research Site
- Valencia 46014 Spain
- Research Site
- Birmingham B15 2TH United Kingdom
- Research Site
- Glasgow G12 0YN United Kingdom
- Research Site
- Guildford CU2 7XX United Kingdom
- Research Site
- London EC1A 7BE United Kingdom
- Research Site
- London NW1 2PG United Kingdom
- Research Site
- London SE1 9RY United Kingdom
- Research Site
- Sheffield S10 2RX United Kingdom
- Research Site
- Southampton SO16 6YD United Kingdom
View trial on ClinicalTrials.gov