Esophageal Squamous Cell Carcinoma
Conditions
Keywords
Locally Advanced unresectable ESCC, PD-L1, Durvalumab
Brief summary
This is a Phase III, randomized, double-blind, placebo-controlled, multi-center international study to assess the efficacy and safety of durvalumab administered concurrently with dCRT in patients with locally advanced, unresectable esophageal squamous cell carcinoma (ESCC).
Detailed description
Approximately 600 patients with locally advanced, unresectable ESCC (AJCC 8th cStage II-IVA) will be randomized in a 2:1 ratio to receive either durvalumab + dCRT or placebo + dCRT. The primary objectives of this study are to assess the efficacy of durvalumab + dCRT compared with placebo + dCRT in terms of progression free survival (PFS, per RECIST 1.1 as assessed by BICR) in PD-L1 High population.
Interventions
DRUGDurvalumab
Durvalumab intravenous infusion
DRUGPlacebo
Durvalumab matching placebo for intravenous infusion
DRUGcisplatin + fluorouracil
cisplatin + fluorouracil, as per Standard of Care
cisplatin + capecitabine, as per Standard of Care
RADIATIONRadiation
50-64Gy in total
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor, excluding supply chain management personnel, will remain blinded.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years or older at the time of signing the ICF. * Histologically or cytologically confirmed esophageal squamous cell carcinoma, and present with locally advanced disease (Stage II-IVA). * Unresectable or refusing surgery, and has been deemed suitable for definitive chemoradiation therapy. * Patients with at least an evaluable lesion per RECIST 1.1. * Mandatory provision of available tumor tissue for PD-L1 expression analysis. * ECOG PS 0 or 1. * Adequate organ and marrow function. * Life expectancy of more than 3 months.
Exclusion criteria
* Histologically or cytologically confirmed small cell esophageal carcinoma, esophageal adenocarcinoma or other mixed carcinoma. * Prior anti-cancer treatment for ESCC. * Patient with a great risk of perforation and massive bleeding. * History of allogeneic organ transplantation. * Active or prior documented autoimmune or inflammatory disorders. * Uncontrolled intercurrent illness. * History of another primary malignancy. * Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus. * Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) per RECIST 1.1 as assessed by BICR | up to approximately 56 months | To assess the efficacy in terms of PFS in PD-L1 High population |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | up to approximately 72 months | To assess the efficacy in terms of OS in all randomized patients and in PD-L1 High population until the date of death |
| Progression free survival (PFS) per RECIST 1.1 as assessed by BICR | up to approximately 56 months | To assess the efficacy in terms of PFS in all randomized patients. |
Countries
Belgium, Brazil, Canada, China, France, Japan, Mexico, Poland, Russia, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United States, Vietnam
Contacts
PRINCIPAL_INVESTIGATORLuhua Wang, MD
Cancer Hospital of Chinese Academy of Medical Science
PRINCIPAL_INVESTIGATORNabil Saba, MD
Department of Hematology and Medical Oncology, Emory University
Outcome results
None listed