About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Single group
Treatments tested in this trial
Durvalumab
DrugAnti- PD-L1 Antibody.
Methotrexate
DrugChemotherapy agent.
Vinblastine
DrugChemotherapy agent
Doxorubicin
DrugChemotherapy agent
Cisplatin
DrugChemotherapy agent
Durvalumab
DrugAnti- PD-L1 Antibody (discontinued to further enrollment)
Gemcitabine
DrugChemotherapy agent (discontinued to further enrollment)
Cisplatin
DrugChemotherapy agent (discontinued to further enrollment)
Treatment groups
Trial outcomes
Primary outcomes
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
Secondary outcomes
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
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.
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.
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.
Sponsors and contacts
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