Perioperative Durvalumab With Neoadjuvant ddMVAC or Gemcitabine/Cisplatin in Patients With Muscle-invasive Bladder Cancer (NIAGARA-2)

Phase 3RecruitingNCT06960577

AstraZeneca150 enrolled

Overview

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.

Not provided

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

150

Conditions

Urinary Bladder Neoplasms Immune Checkpoint Inhibitors Methotrexate Vinblastine Doxorubicin Cisplatin

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

The safety of neoadjuvant durvalumab combined with ddMVAC or gem/cis prior to radical cystectomy (RC).

Incidence of Grade 3 or 4 \[possibly treatment-related adverse events (PRAEs)\] as observed prior to RC.

Time frame: Up to 6 months

Secondary Outcomes

The safety and tolerability of perioperative durvalumab combined with ddMVAC or gem/cis.

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.

Time frame: Up to 2 years

The efficacy of perioperative durvalumab combined with ddMVAC or gem/cis 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.

Time frame: Up to 3 years

The efficacy of perioperative durvalumab combined with ddMVAC or gem/cis 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.

Time frame: Up to 3 years

The efficacy of perioperative durvalumab combined with ddMVAC or gem/cis in terms of OS.

OS is defined as the time from first neoadjuvant durvalumab + chemotherapy until death due to any cause.

Time frame: Up to 3 years

The efficacy of neoadjuvant durvalumab combined with ddMVAC or gem/cis followed by RC in terms of pathologic 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.

Time frame: Up to 3 years

The efficacy of neoadjuvant durvalumab combined with ddMVAC or gem/cis 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.

Time frame: Up to 3 years

Perioperative Durvalumab With Neoadjuvant ddMVAC or Gemcitabine/Cisplatin in Patients With Muscle-invasive Bladder Cancer (NIAGARA-2)

Overview

Conditions

Interventions

Eligibility

Locations (59)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts