Durvalumab+ Gemcitabine/Cisplatin (Neoadjuvant Treatment) and Durvalumab (Adjuvant Treatment) in Patients With MIBC

Phase 3Active Not RecruitingNCT03732677

AstraZeneca1,063 enrolled

Overview

A Global Study to Determine the Efficacy and Safety of Durvalumab in Combination with Gemcitabine+Cisplatin for Neoadjuvant Treatment and Durvalumab Alone for Adjuvant Treatment in Patients with Muscle-Invasive Bladder Cancer

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,063

Conditions

Muscle Invasive Bladder Cancer

Interventions

DurvalumabDRUG

Anti- PD-L1 Antibody

CisplatinDRUG

Chemotherapy Agent

GemcitabineDRUG

Chemotherapy agent

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

Inclusion: * Patient resectable muscle-invasive bladder cancer with clinical stage T2-T4aN0/1M0 with transitional and mixed transitional cell histology * Patients must be planning to undergo a radical cystectomy * Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC * ECOG performance status of 0 or 1 * Must have a life expectancy of at least 12 weeks at randomization Exclusion: * Evidence of lymph node (N2-N3) or metastatic (M1) disease at time of screening. * Prior pelvic radiotherapy treatment within 2 years of randomization to study * Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin \[BCG\]), including but not limited to other anti-CTLA-4, anti-PD-1, anti PD-L1, or anti-PD-L2 antibodies. * Current or prior use of immunosuppressive medication within 14 days before the first dose of investigational product (IP). The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent; Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) * Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. * Uncontrolled intercurrent illness * Active infection including Tuberculosis, Hepatitis B, Hepatitis C, and Human Immunodeficiency

Locations (188)

Outcomes

Primary Outcomes

Pathologic Complete Response (pCR) Rates at Time of Cystectomy

pCR rate is defined as the proportion of patients whose pathological staging was T0N0M0 as assessed per central pathology review using specimens obtained via radical cystectomy following the neoadjuvant treatment. The denominator for pCR will be the number of patients in the FAS.

Time frame: Up to 6 months

Event-free Survival (EFS) Per Central Review Defined as Time From Randomization to Event

EFS is defined as the time from randomization to the first recurrence of disease post radical cystectomy, time of first documented progression in patients who were medically precluded for radical cystectomy, or time of expected surgery in patients who refuse to undergo a radical cystectomy or failure to undergo a radical cystectomy in participants with residual disease, or the time of death due to any cause, whichever occurs first

Time frame: Up to 48 months

Secondary Outcomes

Event-free Survival at 24 Months (EFS24) Per Central Review Defined as Time From Randomization to Event

EFS24 is defined as the Kaplan-Meier estimate of EFS at 24 months after randomization, as assessed per blinded independent central review or by central pathology review if a biopsy is required for a suspected new lesion, and per local investigator or local biopsy review if a biopsy is required for a suspected new lesion

Time frame: Up to 24 months

Proportion of Patients Who Undergo Cystectomy

The proportion of patients who undergo cystectomy is defined as the proportion patients who undergo radical cystectomy after the neoadjuvant treatment. The denominator will be patients in the FAS.

Time frame: Up to 6 months

Overall Survival

OS is defined as the time from the date of randomization until death due to any cause regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy (i.e., date of death or censoring - date of randomization + 1)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Research Site

Birmingham, Alabama, United States

Research Site

Los Angeles, California, United States

Research Site

Palo Alto, California, United States

Research Site

New Haven, Connecticut, United States

Research Site

Chicago, Illinois, United States

Research Site

Geneva, Illinois, United States

Research Site

Iowa City, Iowa, United States

Research Site

Westwood, Kansas, United States

Research Site

Louisville, Kentucky, United States

Research Site

New Orleans, Louisiana, United States

...and 178 more locations

Immunogenicity of Durvalumab When Used in Combination With Gemcitabine/Cisplatin as Measured by Presence of Antidrug Antibodies (ADA)

Whole blood samples for assessing ADA for durvalumab in serum were collected from patients undergoing durvalumab treatment, following the specified assessment schedule. ADA prevalence is the proportion of patients with a positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA includes both treatment-induced and treatment-boosted ADA. Its incidence is the proportion of patients with treatment-emergent ADA positivity. Treatment-boosted ADA refers to a baseline-positive ADA titer that increased ≥4-fold during the study. Persistently positive patients have at least two post-baseline ADA-positive readings, with at least 16 weeks between the first and last, or an ADA-positive result at the final assessment. This includes baseline-positive patients meeting these criteria. Transiently positive is defined by at least one post-baseline ADA-positive reading without being persistently positive, including baseline-positive patients meeting these terms.

Time frame: Up to 12 months