Durvalumab+ Gemcitabine/Cisplatin (Neoadjuvant Treatment) and Durvalumab (Adjuvant Treatment) in Patients With MIBC (NIAGARA)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Muscle Invasive Bladder Cancer
• Intervention / Treatment: Drug: Durvalumab; Drug: Cisplatin; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 1063
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia, 4122
    • Research Site
  • Elizabeth Vale, Australia, 5112
    • Research Site
  • Macquarie University, Australia, 2109
    • Research Site
  • Melbourne, Australia, 3004
    • Research Site
  • Murdoch, Australia, 6150
    • Research Site
  • South Brisbane, Australia, 4101
    • Research Site
• Belgium
  • Brugge, Belgium, 8000
    • Research Site
  • Charleroi, Belgium, 6000
    • Research Site
  • Kortrijk, Belgium, 8500
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
  • Roeselare, Belgium, 8800
    • Research Site
• Brazil
  • Barretos, Brazil, 14784-400
    • Research Site
  • Porto Alegre, Brazil, 90610-000
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Porto Alegre, Brazil, 90020-090
    • Research Site
  • Porto Alegre, Brazil, 90470-340
    • Research Site
  • Rio de Janeiro, Brazil, 20231-050
    • Research Site
  • Santa Maria, Brazil, 97015-450
    • Research Site
  • Sao Paulo, Brazil, 01509-900
    • Research Site
  • Sao Paulo, Brazil, 01323-903
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
  • São Paulo, Brazil, 03102-002
    • Research Site
  • São Paulo, Brazil, 01246-000
    • Research Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Research Site
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Research Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Research Site
    • Toronto, Ontario, Canada, M5G IX6
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 0C2
      • Research Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Research Site
• Chile
  • Antofagasta, Chile, 1267348
    • Research Site
  • Puerto Montt, Chile, 5480000
    • Research Site
  • Santiago, Chile, 7520349
    • Research Site
  • Temuco, Chile, 4810218
    • Research Site
  • Temuco, Chile, 4810469
    • Research Site
  • Viña del Mar, Chile, 2540488
    • Research Site
• Czechia
  • Brno, Czechia, 656 53
    • Research Site
  • Brno, Czechia, 656 91
    • Research Site
  • Hradec Kralove, Czechia, 500 05
    • Research Site
  • Olomouc, Czechia, 77900
    • Research Site
  • Praha, Czechia, 140 59
    • Research Site
  • Praha 2, Czechia, 128 08
    • Research Site
  • Praha 8, Czechia, 180 81
    • Research Site
• France
  • Angers Cedex 01, France, 49033
    • Research Site
  • Dijon, France, 21079
    • Research Site
  • Grenoble Cedex 09, France, 38043
    • Research Site
  • Montpellier, France, 34070
    • Research Site
  • Nimes, France, 30029
    • Research Site
  • Pierre Benite, France, 69495
    • Research Site
  • Poitiers Cedex, France, 86021
    • Research Site
  • Rouen, France, F-76031 CE
    • Research Site
• Germany
  • Bergisch Gladbach, Germany, 51465
    • Research Site
  • Bonn, Germany, 53127
    • Research Site
  • Erlangen, Germany, 91054
    • Research Site
  • Göttingen, Germany, 37075
    • Research Site
  • Herne, Germany, 44625
    • Research Site
  • Jena, Germany, 07747
    • Research Site
  • Köln, Germany, 50937
    • Research Site
  • Magdeburg, Germany, 39120
    • Research Site
  • Mannheim, Germany, 68167
    • Research Site
  • Münster, Germany, 48149
    • Research Site
  • Nürnberg, Germany, 90491
    • Research Site
  • Oldenburg, Germany, 23758
    • Research Site
  • Regensburg, Germany, 93053
    • Research Site
  • Ulm, Germany, 89081
    • Research Site
  • Würzburg, Germany, 97080
    • Research Site
• Israel
  • Haifa, Israel, 31096
    • Research Site
  • Jerusalem, Israel, 91120
    • Research Site
  • Kfar Saba, Israel, 95847
    • Research Site
  • Petach-Tikva, Israel, 4941492
    • Research Site
  • Ramat Gan, Israel, 52621
    • Research Site
• Italy
  • Bari, Italy, 70124
    • Research Site
  • Bologna, Italy, 40138
    • Research Site
  • Firenze, Italy, 50134
    • Research Site
  • Milano, Italy, 20132
    • Research Site
  • Milano, Italy, 20133
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Orbassano, Italy, 10043
    • Research Site
  • Pozzuoli, Italy, 80078
    • Research Site
  • Verona, Italy, 37126
    • Research Site
• Japan
  • Bunkyo-ku, Japan, 113-8603
    • Research Site
  • Fukuoka, Japan, 812-8582
    • Research Site
  • Fukuoka-shi, Japan, 811-1347
    • Research Site
  • Hirosaki-shi, Japan, 036-8563
    • Research Site
  • Hiroshima-shi, Japan, 730-8518
    • Research Site
  • Kanazawa-shi, Japan, 920-8641
    • Research Site
  • Koto-ku, Japan, 135-8550
    • Research Site
  • Kumamoto-shi, Japan, 860-0008
    • Research Site
  • Miyazaki-city, Japan, 889-1692
    • Research Site
  • Nagasaki-shi, Japan, 852-8501
    • Research Site
  • Nagoya-shi, Japan, 466-8560
    • Research Site
  • Niigata-shi, Japan, 951-8520
    • Research Site
  • Osaka-shi, Japan, 541-8567
    • Research Site
  • Osaka-shi, Japan, 545-8586
    • Research Site
  • Osakasayama-shi, Japan, 589-8511
    • Research Site
  • Sendai-shi, Japan, 980-0872
    • Research Site
  • Toyama-shi, Japan, 930-0194
    • Research Site
  • Tsukuba-shi, Japan, 305-8576
    • Research Site
  • Yokohama-shi, Japan, 241-8515
    • Research Site
  • Yokohama-shi, Japan, 232-0024
    • Research Site
• Korea, Republic of
  • Daegu, Korea, Republic of, 41404
    • Research Site
  • Goyang-si, Korea, Republic of, 10408
    • Research Site
  • Gyeonggi-do, Korea, Republic of, 13620
    • Research Site
  • Incheon, Korea, Republic of, 21565
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 136-705
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Research Site
  • Amsterdam, Netherlands, 1081 HV
    • Research Site
  • Breda, Netherlands, 4818 CK
    • Research Site
  • Rotterdam, Netherlands, 3015 GD
    • Research Site
• Philippines
  • Baguio City, Philippines, 2600
    • Research Site
  • Cebu, Philippines, 6000
    • Research Site
  • Davao City, Philippines, 8000
    • Research Site
  • Makati, Philippines, 1229
    • Research Site
  • Manila, Philippines, 1015
    • Research Site
  • Quezon City, Philippines, 1104
    • Research Site
  • Quezon City, Philippines, 1101
    • Research Site
• Poland
  • Bialystok, Poland, 15-027
    • Research Site
  • Gdańsk, Poland, 80-214
    • Research Site
  • Grudziądz, Poland, 86-300
    • Research Site
  • Koszalin, Poland, 75-581
    • Research Site
  • Kraków, Poland, 30-510
    • Research Site
  • Olsztyn, Poland, 10-228
    • Research Site
  • Ostrołęka, Poland, 07-410
    • Research Site
  • Poznan, Poland, 60-693
    • Research Site
  • Warszawa, Poland, 02-781
    • Research Site
  • Wroclaw, Poland, 53-413
    • Research Site
• Russian Federation
  • Krasnoyarsk, Russian Federation, 660133
    • Research Site
  • Moscow, Russian Federation, 105077
    • Research Site
  • Nizhniy Novgorod, Russian Federation, 603074
    • Research Site
  • Novosibirsk, Russian Federation, 630007
    • Research Site
  • Samara, Russian Federation, 443031
    • Research Site
  • St Petersburg, Russian Federation, 194044
    • Research Site
  • St. Petersburg, Russian Federation, 197022
    • Research Site
  • St. Petersburg, Russian Federation, 194017
    • Research Site
  • St. Petersburg, Russian Federation, 194354
    • Research Site
  • Ufa, Russian Federation, 450000
    • Research Site
  • Vologda, Russian Federation, 160012
    • Research Site
• Spain
  • Badalona, Spain, 08916
    • Research Site
  • Barcelona, Spain, 08035
    • Research Site
  • Córdoba, Spain, 14004
    • Research Site
  • Las Palmas de Gran Canaria, Spain, 35016
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Santander, Spain, 39008
    • Research Site
  • Sevilla, Spain, 41013
    • Research Site
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taichung, Taiwan, 404
    • Research Site
  • Tainan, Taiwan, 704
    • Research Site
  • Tainan, Taiwan, 710
    • Research Site
  • Taipei, Taiwan, 11217
    • Research Site
  • Taipei City, Taiwan, 10050
    • Research Site
  • Taoyuan City, Taiwan, 333
    • Research Site
• Turkey
  • Ankara, Turkey, 06590
    • Research Site
  • Edirne, Turkey, 22030
    • Research Site
  • Istanbul, Turkey, 34030
    • Research Site
  • Izmir, Turkey
    • Research Site
  • Karsiyaka, Turkey, 35575
    • Research Site
  • İstanbul, Turkey, 34457
    • Research Site
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XR
    • Research Site
  • London, United Kingdom, E1 1BB
    • Research Site
  • Nottingham, United Kingdom, NG5 1PB
    • Research Site
  • Sheffield, United Kingdom, S10 2SJ
    • Research Site
  • Wirral, United Kingdom, CH63 4JY
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Research Site
  • California
    • Los Angeles, California, United States, 90095
      • Research Site
    • Palo Alto, California, United States, 94304
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
    • Geneva, Illinois, United States, 60134
      • Research Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Research Site
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Research Site
  • Maryland
    • Towson, Maryland, United States, 21204
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
    • Detroit, Michigan, United States, 48201
      • Research Site
  • New York
    • New York, New York, United States, 10029
      • Research Site
    • Rochester, New York, United States, 14642
      • Research Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • Research Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Ho Chi Minh, Vietnam, 700000
    • Research Site
  • Hochiminh, Vietnam, 70000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion:

• 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

Exclusion:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Chemotherapy + Durvalumab	Drug: Durvalumab; Anti- PD-L1 Antibody; Drug: Cisplatin; Chemotherapy Agent; Drug: Gemcitabine; Chemotherapy agent
Active Comparator: Arm 2; Chemotherapy alone	Drug: Cisplatin; Chemotherapy Agent; Drug: Gemcitabine; Chemotherapy agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathologic complete response (pCR) rates at time of cystectomy	Up to 6 months
Event-free survival (EFS) per central review defined as time from randomization to event	Up to 48 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients who achieve <P2 at time of cystectomy	Up to 6 months
EFS at 24 months (EFS24) defined as time from randomization to event	Up to 24 months
Proportion of patients who undergo cystectomy	Up to 6 months
Overall survival rate at 5 years	Up to 60 months
PFS2 defined as time from randomization to event following subsequent therapy	Up to 84 months
Safety and Tolerability as evaluated by adverse events occurring throughout the study	Up to 84 months
Immunogenicity of durvalumab when used in combination with gemcitabine/cisplatin as measured by presence of antidrug antibodies (ADA)	Up to 12 months
Overall Survival	Up to 84 months
Metastasis-free survival per investigator assessment or local biopsy review.	Up to 48 months
Disease-specific survival per investigator assessment or local biopsy review.	up to 48 months
Disease-free survival	Up to 48 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2018
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: October 5, 2018
• First Submitted That Met QC Criteria: November 5, 2018
• First Posted (Actual): November 6, 2018

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; PD-L1; Durvalumab (MEDI4736); Bladder Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab; Gemcitabine
• Other Study ID Numbers: D933RC00001; 2018-001811-59 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No