Urinary Bladder NeoplasmsPhase 2NCT06960577
Perioperative Durvalumab With Neoadjuvant ddMVAC in Patients With Muscle-Invasive Bladder Cancer (NIAGARA-2)
A Phase 2 study testing Durvalumab, Methotrexate and Vinblastine in people with Urinary Bladder Neoplasms and Immune Checkpoint Inhibitors, run by AstraZeneca at 59 sites in 7 countries.
Trial summary
The Phase II NIAGARA-2 study aims to expand on the data from the Phase III NIAGARA study by investigating perioperative durvalumab in combination with cisplatin based neoadjuvant chemotherapy in a clinical practice setting. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urinary Bladder Neoplasms, Immune Checkpoint Inhibitors, Methotrexate
- What is being tested?
- Durvalumab, Methotrexate and Vinblastine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 59 sitesin 7 countries
- Study dates
- 15 May 2025to 30 Aug 2028
- Phase
- Phase 2
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants with clinical tumour stage T2-T4aN0/1M0 or T1N1M0 with transitional or mixed transitional cell histology
- Participants must be planning to undergo radical cystectomy
- Participants who have not received prior systemic chemotherapy or immunotherapy for treatment of muscle-invasive bladder cancer
- ECOG performance status of 0 or 1
- Minimum life expectancy of 12 weeks at first dose of study medication
Who cannot join
- Evidence of lymph node (N2-N3) or metastatic (M1) disease
- Inoperable tumour(s) with fixation to the pelvic wall on clinical examination
- Prior exposure to immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD 1, anti-PD L1 and anti-PD-L2 antibodies, excluding Bacillus Calmette-Guérin
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab
- Any concomitant medication known to be contraindicated with ddMVAC.
- Uncontrolled intercurrent illness.
Trial locations and contacts
59 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
59 sites in 7 countries
France20 sites, 17 recruiting
- Recruiting
Research Site
Angers, 49055
- Withdrawn
Research Site
Angers, 49933
- Recruiting
Research Site
Bordeaux, 33075
- Recruiting
Research Site
Chambray-lès-Tours, 37170
- Withdrawn
Research Site
Dijon, 21079
- Recruiting
Research Site
Lille, 59037
- Recruiting
Research Site
Lyon, 69008
- Recruiting
Research Site
Marseille, 13009
- Recruiting
Research Site
Montpellier, 34070
- Recruiting
Research Site
Nice, 06189
- Recruiting
Research Site
Nîmes, 30029
- Recruiting
Research Site
Paris, 75010
- Recruiting
Research Site
Paris, 75900
- Recruiting
Research Site
Pierre-Bénite, 69310
- Recruiting
Research Site
Poitiers, 86021
- Recruiting
Research Site
Quint-Fonsegrives, 31130
- Recruiting
Research Site
Rennes, 35000
- Withdrawn
Research Site
Rouen, 76230
- Recruiting
Research Site
Strasbourg, 67033
- Recruiting
Research Site
Suresnes, 92150
Spain10 sites, 9 recruiting
- Recruiting
Research Site
Barcelona, 08025
- Recruiting
Research Site
Barcelona, 08035
- Recruiting
Research Site
Barcelona, 08036
- Recruiting
Research Site
Barcelona, 8003
- Recruiting
Research Site
Girona, 17007
- Withdrawn
Research Site
Las Palmas de Gran Canaria, 35016
- Recruiting
Research Site
Lugo, 27003
- Recruiting
Research Site
Madrid, 28033
- Recruiting
Research Site
Madrid, 28040
- Recruiting
Research Site
Santiago de Compostela, 15706
Australia9 sites, 8 recruiting
- Recruiting
Research Site
Chermside, 4032
- Recruiting
Research Site
Elizabeth Vale, 5112
- Recruiting
Research Site
Heidelberg, 3084
- Recruiting
Research Site
Hong Kong
- Recruiting
Research Site
Kogarah, 2217
- Recruiting
Research Site
Macquarie University, 2109
- Recruiting
Research Site
Murdoch, 6150
- Withdrawn
Research Site
Port Macquarie, 2444
- Recruiting
Research Site
St Leonards, 2065
Brazil8 sites, 4 recruiting
- Recruiting
Research Site
Barretos, 14784-400
- Withdrawn
Research Site
Jaú, 17210-080
- Withdrawn
Research Site
Natal, 59075-740
- Recruiting
Research Site
Porto Alegre, 91350-200
- Withdrawn
Research Site
Rio de Janeiro, 20230-130
- Recruiting
Research Site
Santo André, 09060-650
- Withdrawn
Research Site
São José do Rio Preto, 15090-000
- Recruiting
Research Site
São Paulo, 01246-000
Canada6 sites, 5 recruiting
- Recruiting
Research Site
Hamilton, Ontario, L8V 5C2
- Recruiting
Research Site
London, Ontario, N6A 5W9
- Recruiting
Research Site
Montreal, Quebec, H3T 1E2
- Withdrawn
Research Site
Ottawa, Ontario, K1H 8L6
- Recruiting
Research Site
Québec, Quebec, G1J 1Z4
- Recruiting
Research Site
Sherbrooke, Quebec, J1H 5N4
Italy3 sites, 3 recruiting
- Recruiting
Research Site
Florence, 50139
- Recruiting
Research Site
Orbassano, 10043
- Recruiting
Research Site
Roma, 00144
Netherlands3 sites, 2 recruiting
- Recruiting
Research Site
Amsterdam, 1066CX
- Withdrawn
Research Site
Nijmegen, 6500 HB
- Recruiting
Research Site
Rotterdam, 3015 GD
About this study
Official title: An Open-label, Single-arm, Global Study of Perioperative Durvalumab With Cisplatin-based Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer (NIAGARA-2)
The Phase II NIAGARA-2 study aims to expand on the data from the Phase III NIAGARA study by investigating perioperative durvalumab in combination with cisplatin based neoadjuvant chemotherapy in a clinical practice setting.
Read the detailed description
Not provided
- Conditions
- Urinary Bladder Neoplasms, Immune Checkpoint Inhibitors, Methotrexate, Vinblastine, Doxorubicin, Cisplatin
- Being tested
- Durvalumab, Methotrexate, Vinblastine, Doxorubicin, Cisplatin
- Keywords
- Muscle-invasive Bladder Cancer, Bladder Cancer, Immunotherapy, Durvalumab, Perioperative Durvalumab, ddMVAC, Gemcitabine, Cisplatin
- 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.
MethotrexateDrug
Chemotherapy agent.
VinblastineDrug
Chemotherapy agent
DoxorubicinDrug
Chemotherapy agent
CisplatinDrug
Chemotherapy agent
DurvalumabDrug
Anti- PD-L1 Antibody (discontinued to further enrollment)
GemcitabineDrug
Chemotherapy agent (discontinued to further enrollment)
CisplatinDrug
Chemotherapy agent (discontinued to further enrollment)
| Study group | Role | What they receive |
|---|---|---|
| ddMVAC cohort | Experimental | Durvalumab + chemotherapy, approximately 120 participants Receives: Drug: Durvalumab; Drug: Methotrexate; Drug: Vinblastine; Drug: Doxorubicin; Drug: Cisplatin |
| gem/cis cohort | Experimental | Durvalumab + chemotherapy; approximately 30 participants; closed to further enrolment Receives: Drug: Durvalumab; Drug: Gemcitabine; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of neoadjuvant durvalumab combined with ddMVAC prior to radical cystectomy (RC).
Incidence of Grade 3 or 4 possibly treatment-related adverse events observed from the first dose of neoadjuvant study treatment until RC or the corresponding prespecified endpoint-window end date for participants who do not undergo RC
Measured: Up to 6 months
Secondary outcomes (6)
The safety and tolerability of perioperative durvalumab combined with neoadjuvant therapy
Incidence, severity, nature, seriousness, outcome and causality of treatment-emergent adverse events, including PRAEs, adverse events of special interest, immune-mediated adverse events and serious adverse events; adverse events leading to study treatment interruption or discontinuation; and clinically relevant laboratory abnormalities
Measured: Up to 2 years
The efficacy of perioperative durvalumab combined with ddMVAC in terms of event-free survival (EFS).
EFS is defined as the time from first neoadjuvant durvalumab + chemotherapy treatment until the earliest occurrence of any of the following events:
- First recurrence of disease after RC
- First documented progression in participants who were medically precluded from RC
- Time of expected surgery in participants who refuse to undergo RC or failure to undergo RC in participants with residual disease
- Death due to any cause.
Data from the legacy Gem/Cis cohort will be summarized for completeness, where applicable.
Measured: Up to 3 years
The efficacy of perioperative durvalumab combined with ddMVAC in terms of disease-free survival (DFS).
DFS is defined as the time from the date of RC to the earliest of the first recurrence of disease post RC or death due to any cause.
Data from the legacy Gem/Cis cohort will be summarized for completeness, where applicable.
Measured: Up to 3 years
The efficacy of perioperative durvalumab combined with ddMVAC in terms of OS.
OS is defined as the time from first neoadjuvant durvalumab + chemotherapy until death due to any cause.
Data from the legacy Gem/Cis cohort will be summarized for completeness, where applicable.
Measured: Up to 3 years
The efficacy of neoadjuvant durvalumab combined with ddMVAC followed by RC in terms of pathological complete response (pCR).
pCR rate is defined as the proportion of participants whose pathologic staging is T0N0M0 as assessed per local pathology review using specimens obtained via RC.
Data from the legacy Gem/Cis cohort will be summarized for completeness, where applicable.
Measured: Up to 3 years
The efficacy of neoadjuvant durvalumab combined with ddMVAC followed by RC in terms of pathologic downstaging (pDS).
pDS rate is defined as the proportion of participants whose pathologic staging is <P2 per local pathology review using specimens obtained via RC.
Data from the legacy Gem/Cis cohort will be summarized for completeness, where applicable.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2025
- Study start15 May 2025
- Primary completion30 Aug 2028 (estimated)
- Study completion30 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urinary Bladder NeoplasmsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06960577
- Sponsor's protocol ID
- D933RC00002
- Status last verified
- Oct 2026
- First submitted
- 29 Apr 2025
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.