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).
Full Title of Study: “A Phase III, Randomized, Double-Blind, Placebo Controlled, Multi-Center, International Study of Durvalumab Given Concurrently With Definitive Chemoradiation Therapy in Patients With Locally Advanced, Unresectable Esophageal Squamous Cell Carcinoma (KUNLUN)”
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Treatment
- Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Study Primary Completion Date: June 30, 2025
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 all randomized patients (intent-to-treat [ITT] population) and PFS in patients with PD-L1 high tumors (PD-L1 High population).
- Drug: Durvalumab
- Durvalumab intravenous infusion
- Drug: Placebo
- Durvalumab matching placebo for intravenous infusion
- Drug: cisplatin + fluorouracil
- cisplatin + fluorouracil, as per Standard of Care
- Drug: cisplatin + capecitabine
- cisplatin + capecitabine, as per Standard of Care
- Radiation: Radiation
- 50-64Gy in total
Arms, Groups and Cohorts
- Experimental: Arm 1: Durvalumab + definitive CRT
- Durvalumab + concurrent chemoradiation
- Placebo Comparator: Arm 2: Placebo + definitive CRT
- Placebo + concurrent chemoradiation
Clinical Trial Outcome Measures
- Progression free survival (PFS) per RECIST 1.1 as assessed by BICR
- Time Frame: up to approximately 56 months
- To assess the efficacy in terms of PFS in all randomized patients and in patients with PD-L1 High tumors until disease progression
- Overall survival (OS)
- Time Frame: up to approximately 72 months
- To assess the efficacy in terms of OS in all randomized patients and in patients with PD-L1 High tumors until the date of death
Participating in This Clinical Trial
- 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 and has been deemed suitable for definitive chemoradiation therapy.
- Patients with at least 1 lesion that qualifies as a RECIST 1.1 Target Lesion at baseline.
- 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.
- Histologically or cytologically confirmed small cell esophageal carcinoma, esophageal adenocarcinoma or other mixed carcinoma.
- Prior anti-cancer treatment, including but not limited to, chemotherapy and/or radiation therapy, immunotherapy, and investigational agents.
- 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.
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: 130 Years
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- Provider of Information About this Clinical Study
- Overall Official(s)
- Luhua Wang, MD, Principal Investigator, Cancer Hospital of Chinese Academy of Medical Science
- Overall Contact(s)
- AstraZeneca Clinical Study Information Center, 1-877-240-9479, email@example.com
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