Perioperative Durvalumab With Neoadjuvant ddMVAC or Gemcitabine/Cisplatin in Patients With Muscle-invasive Bladder Cancer (NIAGARA-2)
- Conditions
- Urinary Bladder NeoplasmsImmune Checkpoint InhibitorsMethotrexateVinblastineDoxorubicinCisplatinGemcitabine
- Interventions
- Registration Number
- NCT06960577
- Lead Sponsor
- AstraZeneca
- 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
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 150
- 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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ddMVAC cohort Durvalumab Durvalumab + chemotherapy ddMVAC cohort Methotrexate Durvalumab + chemotherapy ddMVAC cohort Vinblastine Durvalumab + chemotherapy ddMVAC cohort Doxorubicin Durvalumab + chemotherapy gem/cis cohort Durvalumab Durvalumab + chemotherapy ddMVAC cohort Cisplatin Durvalumab + chemotherapy gem/cis cohort Cisplatin Durvalumab + chemotherapy gem/cis cohort Gemcitabine Durvalumab + chemotherapy
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (1)
Research Site
🇪🇸Santiago de Compostela, Spain