A phase II trial to evaluate safety and efficacy of adding durvalumab (MEDI4736) to standard neoadjuvant radiochemotherapy and of adjuvant durvalumab +/- tremelimumab in locally advanced esophageal adenocarcinoma and to evaluate biomarkers predictive for response to immune checkpoint inhibition
Short Study Title: RICE - Radio-Immuno-Chemotherapy of Cancer of the Esophagus Study Phase: Phase II Research hypothesis: The investigators aim at evaluating if (I) esophageal cancer is susceptible to immunotherapeutic approaches based on interference with the PD1 / PDL1 axis, if (II) treatment of locally advanced tumors by immunotherapeutic approaches increases cure rate and if (III) combination with radiotherapy is feasible and increases anti-tumor immunity. Primary Objectives: The primary objective is to evaluate safety and efficacy (measured by an increase of pathological complete response rate from 20% to 35%) of the fully human monoclonal IgG1 antibody durvalumab targeting the programmed death-ligand 1 (PD-L1) in combination with neoadjuvant radiochemotherapy, followed by surgery for locally advanced esophageal cancer and cancer of the gastric esophageal junction (GEJ).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
56
IV Infusion
IV Infusion, Combination with Durvalumab
University of Cologne
Cologne, Germany
Klinikum der Universität München
München, Germany
Evaluation of Safety and efficacy (measured by an increase of pathological complete response rate)
The primary objective is to evaluate safety and efficacy (measured by an increase of pathological complete response rate from 20% to 35%) of the fully human monoclonal IgG1 antibody durvalumab targeting the programmed death-ligand 1 (PD-L1) in combination with neoadjuvant radiochemotherapy, followed by surgery for locally advanced esophageal cancer and cancer of the gastric esophageal junction (GEJ).
Time frame: Calculated once at the end of study (24 months after the end of treatment)
Determination of Best Objective Response (BOR) as defined by RECIST 1.1 and iRECIST criteria after neoadjuvant treatment
To determine the Best Objective Response (BOR) as defined by RECIST 1.1 and iRECIST criteria after neoadjuvant treatment
Time frame: Determined once after neoadjuvant treatment (up to 12 weeks after study start)
Determination of Progression Free Survival (PFS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment
To determine Progression Free Survival (PFS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment. PFS is defined as PFS from treatment start to first detection of disease progression.
Time frame: Until 24 months after the end of treatment
Determination of Disease Free Survival (DFS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment
To determine Disease Free Survival (DFS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment. DFS is defined as DFS from time of surgery to first detection of disease progression.
Time frame: Until 24 months after the end of treatment
Determination of Overall Survival (OS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment
To determine Overall Survival (OS) in durvalumab vs. durvalumab + tremelimumab adjuvant treatment. OS is defined as OS from treatment start to death.
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Time frame: From the study start until the date of death, assessed up to 240 months
Assessment of the subject's esophageal-cancer-related quality of life using the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) questionnaire
To assess the subject's esophageal-cancer-related quality of life using the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) questionnaire. The questionnaire will be done by interview administration at screening, visit 5 during neoadjuvant treatment, before surgery, after randomization before start of adjuvant treatment and after then every 12 weeks at the time of tumor staging also in the follow-up phase.
Time frame: Until 24 months after the end of treatment