Muscle Invasive Bladder CancerPhase 3NIAGARANCT03732677
Durvalumab+ Gemcitabine/Cisplatin (Neoadjuvant Treatment) and Durvalumab (Adjuvant Treatment) in Patients With MIBC
A Phase 3 study testing Durvalumab, Cisplatin and Gemcitabine in people with Muscle Invasive Bladder Cancer, run by AstraZeneca at 188 sites in 22 countries.
Trial summary
A Global Study to Determine the Efficacy and Safety of Durvalumab in Combination with Gemcitabine+Cisplatin for Neoadjuvant Treatment and Durvalumab Alone for Adjuvant Treatment in Patients with Muscle-Invasive Bladder Cancer Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Muscle Invasive Bladder Cancer
- What is being tested?
- Durvalumab, Cisplatin and Gemcitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,063 participants
- Where
- 188 sitesin 22 countries
- Study dates
- 16 Nov 2018to 8 Nov 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient resectable muscle-invasive bladder cancer with clinical stage T2-T4aN0/1M0 with transitional and mixed transitional cell histology
- Patients must be planning to undergo a radical cystectomy
- Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC
- ECOG performance status of 0 or 1
- Must have a life expectancy of at least 12 weeks at randomization
Who cannot join
- Evidence of lymph node (N2-N3) or metastatic (M1) disease at time of screening.
- Prior pelvic radiotherapy treatment within 2 years of randomization to study
- Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin [BCG]), including but not limited to other anti-CTLA-4, anti-PD-1, anti PD-L1, or anti-PD-L2 antibodies.
- 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.
- Uncontrolled intercurrent illness
- Active infection including Tuberculosis, Hepatitis B, Hepatitis C, and Human Immunodeficiency
Trial locations and contacts
188 sites in 22 countries.
188 sites in 22 countries
Japan20 sites
Research Site
Bunkyō City, 113-8603
Research Site
Fukuoka, 811-1347
Research Site
Fukuoka, 812-8582
Research Site
Hirosaki-shi, 036-8563
Research Site
Hiroshima, 730-8518
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Kanazawa, 920-8641
Research Site
Kōtoku, 135-8550
Research Site
Kumamoto, 860-0008
Research Site
Miyazaki, 889-1692
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Nagasaki, 852-8501
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Nagoya, 466-8560
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Niigata, 951-8520
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Osaka, 541-8567
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Osaka, 545-8586
Research Site
Osakasayama-shi, 589-8511
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Sendai, 980-0872
Research Site
Toyama, 930-0194
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Tsukuba, 305-8576
Research Site
Yokohama, 232-0024
Research Site
Yokohama, 241-8515
United States18 sites
Research Site
Ann Arbor, Michigan, 48109
Research Site
Bethlehem, Pennsylvania, 18015
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Birmingham, Alabama, 35294
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Burlington, Vermont, 05401
Research Site
Chicago, Illinois, 60611
Research Site
Detroit, Michigan, 48201
Research Site
Geneva, Illinois, 60134
Research Site
Iowa City, Iowa, 52242
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Los Angeles, California, 90095
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Louisville, Kentucky, 40202
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Milwaukee, Wisconsin, 53226
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New Haven, Connecticut, 06520
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New Orleans, Louisiana, 70112
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New York, New York, 10029
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Palo Alto, California, 94304
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Rochester, New York, 14642
Research Site
Towson, Maryland, 21204
Research Site
Westwood, Kansas, 66205
Germany15 sites
Research Site
Bergisch Gladbach, 51465
Research Site
Bonn, 53127
Research Site
Cologne, 50937
Research Site
Erlangen, 91054
Research Site
Göttingen, 37075
Research Site
Herne, 44625
Research Site
Jena, 07747
Research Site
Magdeburg, 39120
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Mannheim, 68167
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Münster, 48149
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Nuremberg, 90491
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Oldenburg, 23758
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Regensburg, 93053
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Ulm, 89081
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Würzburg, 97080
Brazil12 sites
Research Site
Barretos, 14784-400
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Porto Alegre, 90020-090
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Porto Alegre, 90470-340
Research Site
Porto Alegre, 90610-000
Research Site
Porto Alegre, 91350-200
Research Site
Rio de Janeiro, 20231-050
Research Site
Santa Maria, 97015-450
Research Site
São José do Rio Preto, 15090-000
Research Site
São Paulo, 01246-000
Research Site
São Paulo, 01323-903
Research Site
São Paulo, 01509-900
Research Site
São Paulo, 03102-002
Russia11 sites
Research Site
Krasnoyarsk, 660133
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Moscow, 105077
Research Site
Nizhny Novgorod, 603074
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Novosibirsk, 630007
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Saint Petersburg, 194017
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Saint Petersburg, 194044
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Saint Petersburg, 194354
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Saint Petersburg, 197022
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Samara, 443031
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Ufa, 450000
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Vologda, 160012
Poland10 sites
Research Site
Bialystok, 15-027
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Gdansk, 80-952
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Grudziądz, 86-300
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Koszalin, 75-581
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Krakow, 30-510
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Olsztyn, 10-228
Research Site
Ostrołęka, 07-410
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Poznan, 60-693
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Warsaw, 02-781
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Wroclaw, 53-413
Italy9 sites
Research Site
Bari, 70124
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Bologna, 40138
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Florence, 50134
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Milan, 20132
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Milan, 20133
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Naples, 80131
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Orbassano, 10043
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Pozzuoli, 80078
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Verona, 37126
France8 sites
Research Site
Angers, 49033
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Dijon, 21079
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Grenoble, 38043
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Montpellier, 34070
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Nîmes, 30029
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Pierre-Bénite, 69495
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Poitiers, 86021
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Rouen, F-76031 CE
Spain8 sites
Research Site
Badalona, 08916
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Barcelona, 08035
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Córdoba, 14004
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Las Palmas de Gran Canaria, 35016
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Madrid, 28007
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Madrid, 28041
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Santander, 39008
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Seville, 41013
Taiwan8 sites
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Kaohsiung City, 807
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Taichung, 404
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Taichung, 40705
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Tainan, 704
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Tainan, 710
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Taipei, 10050
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Taipei, 11217
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Taoyuan City, 333
Canada7 sites
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Edmonton, Alberta, T6G 1Z2
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London, Ontario, N6A 5W9
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Montreal, Quebec, H2X 0C2
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Ottawa, Ontario, K1H 8L6
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Sherbrooke, Quebec, J1H 5N4
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Toronto, Ontario, M5G IX6
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Vancouver, British Columbia, V5Z 4E6
Czechia7 sites
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Brno, 656 53
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Brno, 656 91
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Hradec Králové, 500 05
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Olomouc, 77900
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Prague, 128 08
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Prague, 140 59
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Prague, 180 81
Philippines7 sites
Research Site
Baguio City, 2600
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Cebu, 6000
Research Site
Davao City, 8000
Research Site
Makati, 1229
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Manila, 1015
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Quezon City, 1101
Research Site
Quezon City, 1104
South Korea7 sites
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Daegu, 41404
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Goyang-si, 10408
Research Site
Gyeonggi-do, 13620
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Incheon, 21565
Research Site
Seoul, 03080
Research Site
Seoul, 05505
Research Site
Seoul, 136-705
Australia6 sites
Research Site
Brisbane, 4122
Research Site
Elizabeth Vale, 5112
Research Site
Macquarie University, 2109
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Melbourne, 3004
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Murdoch, 6150
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South Brisbane, 4101
Belgium6 sites
Research Site
Bruges, 8000
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Charleroi, 6000
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Kortrijk, 8500
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Leuven, 3000
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Liège, 4000
Research Site
Roeselare, 8800
Chile6 sites
Research Site
Antofagasta, 1267348
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Port Montt, 5480000
Research Site
Santiago, 7520349
Research Site
Temuco, 4810218
Research Site
Temuco, 4810469
Research Site
Viña del Mar, 2540488
Turkey (Türkiye)6 sites
Research Site
Ankara, 06590
Research Site
Cordaleo, 35575
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Edirne, 22030
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Istanbul, 34030
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Istanbul, 34457
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Izmir
Israel5 sites
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Haifa, 31096
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Jerusalem, 91120
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Kfar Saba, 95847
Research Site
Petah Tikva, 4941492
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Ramat Gan, 52621
United Kingdom5 sites
Research Site
Edinburgh, EH4 2XR
Research Site
London, E1 1BB
Research Site
Metropolitan Borough of Wirral, CH63 4JY
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Nottingham, NG5 1PB
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Sheffield, S10 2SJ
Netherlands4 sites
Research Site
Amsterdam, 1066 CX
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Amsterdam, 1081 HV
Research Site
Breda, 4818 CK
Research Site
Rotterdam, 3015 GD
Vietnam3 sites
Research Site
Hanoi, 100000
Research Site
Ho Chi Minh City, 700000
Research Site
Hochiminh, 70000
About this study
Official title: A Phase III, Randomized, Open-Label, Multi-Center, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Gemcitabine+Cisplatin for Neoadjuvant Treatment Followed by Durvalumab Alone for Adjuvant Treatment in Patients With Muscle-Invasive Bladder Cancer.
A Global Study to Determine the Efficacy and Safety of Durvalumab in Combination with Gemcitabine+Cisplatin for Neoadjuvant Treatment and Durvalumab Alone for Adjuvant Treatment in Patients with Muscle-Invasive Bladder Cancer
- Conditions
- Muscle Invasive Bladder Cancer
- Being tested
- Durvalumab, Cisplatin, Gemcitabine
- Keywords
- Bladder Cancer, Immunotherapy, PD-L1, Durvalumab (MEDI4736)
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Anti- PD-L1 Antibody
CisplatinDrug
Chemotherapy Agent
GemcitabineDrug
Chemotherapy agent
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Chemotherapy + Durvalumab Receives: Drug: Durvalumab; Drug: Cisplatin; Drug: Gemcitabine |
| Arm 2 | Active comparator | Chemotherapy alone Receives: Drug: Cisplatin; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response (pCR) Rates at Time of Cystectomy
pCR rate is defined as the proportion of patients whose pathological staging was T0N0M0 as assessed per central pathology review using specimens obtained via radical cystectomy following the neoadjuvant treatment. The denominator for pCR will be the number of patients in the FAS.
Measured: Up to 6 months
Event-free Survival (EFS) Per Central Review Defined as Time From Randomization to Event
EFS is defined as the time from randomization to the first recurrence of disease post radical cystectomy, time of first documented progression in patients who were medically precluded for radical cystectomy, or time of expected surgery in patients who refuse to undergo a radical cystectomy or failure to undergo a radical cystectomy in participants with residual disease, or the time of death due to any cause, whichever occurs first
Measured: Up to 48 months
Secondary outcomes (6)
Event-free Survival at 24 Months (EFS24) Per Central Review Defined as Time From Randomization to Event
EFS24 is defined as the Kaplan-Meier estimate of EFS at 24 months after randomization, as assessed per blinded independent central review or by central pathology review if a biopsy is required for a suspected new lesion, and per local investigator or local biopsy review if a biopsy is required for a suspected new lesion
Measured: Up to 24 months
Proportion of Patients Who Undergo Cystectomy
The proportion of patients who undergo cystectomy is defined as the proportion patients who undergo radical cystectomy after the neoadjuvant treatment. The denominator will be patients in the FAS.
Measured: Up to 6 months
Overall Survival
OS is defined as the time from the date of randomization until death due to any cause regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy (i.e., date of death or censoring - date of randomization + 1)
Measured: Up to 65 months
Metastasis-free Survival Per Investigator Assessment or Local Biopsy Review.
MFS is defined as the time from date of randomization until the first recognition of distant metastases or death, whichever occurs first
Measured: Up to 48 months
Disease-specific Survival Per Investigator Assessment or Local Biopsy Review.
DSS is defined as the time from the date of randomization until death due to bladder cancer
Measured: Up to 48 months
Immunogenicity of Durvalumab When Used in Combination With Gemcitabine/Cisplatin as Measured by Presence of Antidrug Antibodies (ADA)
Whole blood samples for assessing ADA for durvalumab in serum were collected from patients undergoing durvalumab treatment, following the specified assessment schedule. ADA prevalence is the proportion of patients with a positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA includes both treatment-induced and treatment-boosted ADA. Its incidence is the proportion of patients with treatment-emergent ADA positivity. Treatment-boosted ADA refers to a baseline-positive ADA titer that increased ≥4-fold during the study. Persistently positive patients have at least two post-baseline ADA-positive readings, with at least 16 weeks between the first and last, or an ADA-positive result at the final assessment. This includes baseline-positive patients meeting these criteria. Transiently positive is defined by at least one post-baseline ADA-positive reading without being persistently positive, including baseline-positive patients meeting these terms.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2018
- Study start16 Nov 2018
- Primary completion29 Apr 2024
- Study completion8 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Muscle Invasive Bladder CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,063 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03732677
- Sponsor's protocol ID
- D933RC00001
- Other IDs
- 2023-510015-19-00, 2018-001811-59, 2018, 2023
- Acronym
- NIAGARA
- Status last verified
- Oct 2026
- First submitted
- 5 Oct 2018
- Last updated
- 15 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
Powles T, Catto JWF, Galsky MD, Al-Ahmadie H, Meeks JJ, Nishiyama H, Vu TQ, Antonuzzo L, Wiechno P, Atduev V, Kann AG, Kim TH, Suarez C, Chang CH, Roghmann F, Ozguroglu M, Eigl BJ, Oliveira N, Buchler T, Gadot M, Zakharia Y, Armstrong J, Gupta A, Hois S, van der Heijden MS; NIAGARA Investigators. Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer. N Engl J Med. 2024 Nov 14;391(19):1773-1786. doi: 10.1056/NEJMoa2408154. Epub 2024 Sep 15.
PubMed 39282910