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

NCT ID: NCT03528694

Last Updated: 2025-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1018 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-14

Study Completion Date

2028-10-03

Brief Summary

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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

Detailed Description

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

Conditions

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Non-muscle-invasive Bladder Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Durvalumab plus BCG (induction + maintenance)

Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy

Group Type EXPERIMENTAL

Durvalumab (MEDI4736)

Intervention Type BIOLOGICAL

Investigational product

Bacillus Calmette-Guerin (BCG)

Intervention Type BIOLOGICAL

Standard of care

Durvalumab plus BCG (induction only)

Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy

Group Type EXPERIMENTAL

Durvalumab (MEDI4736)

Intervention Type BIOLOGICAL

Investigational product

Bacillus Calmette-Guerin (BCG)

Intervention Type BIOLOGICAL

Standard of care

BCG treatment (Standard of care therapy)

Bacillus Calmette-Guerrin (BCG) standard of care treatment

Group Type ACTIVE_COMPARATOR

Bacillus Calmette-Guerin (BCG)

Intervention Type BIOLOGICAL

Standard of care

Interventions

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Durvalumab (MEDI4736)

Investigational product

Intervention Type BIOLOGICAL

Bacillus Calmette-Guerin (BCG)

Standard of care

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion 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

* 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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Auchenflower, , Australia

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Box Hill, , Australia

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Brisbane, , Australia

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Kogarah, , Australia

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Orange, , Australia

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Parkville, , Australia

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Westmead, , Australia

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Wollongong, , Australia

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Graz, , Austria

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Innsbruck, , Austria

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Linz, , Austria

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Salzburg, , Austria

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Vienna, , Austria

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Brussels, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Roeselare, , Belgium

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Kingston, Ontario, Canada

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Toronto, Ontario, Canada

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Chicoutimi, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Amiens, , France

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Angers, , France

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Bordeaux, , France

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Lyon, , France

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Marseille, , France

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Montpellier, , France

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Strasbourg, , France

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Suresnes, , France

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Berlin, , Germany

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Cologne, , Germany

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Duisburg, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Marburg, , Germany

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Mettmann, , Germany

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Mühlheim An Der Ruhr, , Germany

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München, , Germany

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Münster, , Germany

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Nürtingen, , Germany

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Wesel, , Germany

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Würselen, , Germany

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Zirndorf, , Germany

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Bunkyō City, , Japan

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Fukuoka, , Japan

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Hirosaki-shi, , Japan

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Kanazawa, , Japan

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Kita-gun, , Japan

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Koshigaya-shi, , Japan

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Kōtoku, , Japan

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Matsuyama, , Japan

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Miyazaki, , Japan

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Nagasaki, , Japan

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Nagoya, , Japan

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Okayama, , Japan

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Osaka, , Japan

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Osaka, , Japan

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Osakasayama-shi, , Japan

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Sapporo, , Japan

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Shinjuku-ku, , Japan

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Toyama, , Japan

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Tsukuba, , Japan

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Yokohama, , Japan

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Amsterdam, , Netherlands

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Breda, , Netherlands

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Utrecht, , Netherlands

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Bialystok, , Poland

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Gdansk, , Poland

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Grudziądz, , Poland

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Koszalin, , Poland

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Piotrkow Trybunalski, , Poland

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Poznan, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Wroclaw, , Poland

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Ivanovo, , Russia

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Krasnoyarsk, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Obninsk, , Russia

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Omsk, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Vologda, , Russia

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Yaroslavl, , Russia

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Badajoz, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Elche(Alicante), , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Oviedo, , Spain

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Pamplona, , Spain

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Pozuelo de Alarcón, , Spain

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Seville, , Spain

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Seville, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Birmingham, , United Kingdom

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Glasgow, , United Kingdom

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Guildford, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Sheffield, , United Kingdom

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Southampton, , United Kingdom

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Taunton, , United Kingdom

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Countries

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Australia Austria Belgium Canada France Germany Japan Netherlands Poland Russia Spain United Kingdom

References

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De Santis M, Palou Redorta J, Nishiyama H, Krawczynski M, Seyitkuliev A, Novikov A, Guerrero-Ramos F, Zukov R, Kato M, Kawahara T, Goeman L, Puente J, Hellmis E, Powles T, Radziszewski P, Gust KM, Vasey P, Bigot P, Fradet Y, Hunting J, Armstrong J, Boulos S, Hois S, Shore ND; POTOMAC Investigators. Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial. Lancet. 2025 Nov 8;406(10516):2221-2234. doi: 10.1016/S0140-6736(25)01897-5. Epub 2025 Oct 17.

Reference Type DERIVED
PMID: 41115436 (View on PubMed)

Other Identifiers

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2017-002979-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D419JC00001

Identifier Type: -

Identifier Source: org_study_id

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