Cisplatin, Doxorubicin, Gemcitabine, Immune Checkpoint Inhibitors, Methotrexate, Urinary Bladder Neoplasms, Vinblastine
Conditions
Keywords
Muscle-invasive Bladder Cancer, Bladder Cancer, Immunotherapy, Durvalumab, Perioperative Durvalumab, ddMVAC, Gemcitabine, Cisplatin
Brief summary
The Phase IIIb NIAGARA-2 study aims to expand on the data from the Phase III NIAGARA study by investigating perioperative durvalumab in combination with investigator-selected cisplatin-based neoadjuvant chemotherapy (either ddMVAC or gemcitabine/cisplatin) in a clinical practice setting.
Detailed description
Not provided
Interventions
DRUGDurvalumab
Anti- PD-L1 Antibody.
DRUGMethotrexate
Chemotherapy agent.
DRUGVinblastine
Chemotherapy agent
DRUGDoxorubicin
Chemotherapy agent
DRUGCisplatin
Chemotherapy agent
DRUGGemcitabine
Chemotherapy agent
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with clinical tumour stage T2-T4aN0/1M0 or T1N1M0 with transitional or mixed transitional cell histology * Patients must be planning to undergo radical cystectomy * Patients 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
Exclusion criteria
* 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 to the chemotherapy (ddMVAC or gem/cis). * Uncontrolled intercurrent illness.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The safety of neoadjuvant durvalumab combined with ddMVAC or gem/cis prior to radical cystectomy (RC). | Up to 6 months | Incidence of Grade 3 or 4 \[possibly treatment-related adverse events (PRAEs)\] as observed prior to RC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The safety and tolerability of perioperative durvalumab combined with ddMVAC or gem/cis. | Up to 2 years | Incidence, severity, nature, seriousness, intervention/treatment, outcome, and causality of treatment-emergent adverse events, including PRAEs, adverse events of special interest, immune-mediated adverse events, adverse events (AEs), and serious adverse events; AEs resulting in study treatment interruption and discontinuation; laboratory findings. |
| The efficacy of perioperative durvalumab combined with ddMVAC or gem/cis in terms of event-free survival (EFS). | Up to 3 years | 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. |
| The efficacy of perioperative durvalumab combined with ddMVAC or gem/cis in terms of disease-free survival (DFS). | Up to 3 years | 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. |
| The efficacy of perioperative durvalumab combined with ddMVAC or gem/cis in terms of OS. | Up to 3 years | OS is defined as the time from first neoadjuvant durvalumab + chemotherapy until death due to any cause. |
| The efficacy of neoadjuvant durvalumab combined with ddMVAC or gem/cis followed by RC in terms of pathologic complete response (pCR). | Up to 3 years | 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. |
| The efficacy of neoadjuvant durvalumab combined with ddMVAC or gem/cis followed by RC in terms of pathologic downstaging (pDS). | Up to 3 years | pDS rate is defined as the proportion of participants whose pathologic staging is \<P2 per local pathology review using specimens obtained via RC. |
Countries
Australia, Brazil, Canada, France, Italy, Netherlands, Spain
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed