The present clinical trial is a prospective, investigator-initiated, single-arm, open-label, multicenter phase II trial investigating whether a definite organ preservation therapy consisting of the combination of durvalumab with chemoradiation is an efficient and safe treatment option for early stage, cT1 and cT2N0, esophageal adenocarcinoma with indication for radical surgery.
Patient has given written informed consent.
Patient is, in the investigator's judgement, willing and able to comply with the study protocol including the planned surgical treatment.
Patient is ≥ 18 years of age at time of signing the written informed consent.
cT2 N0 M0 stage or T1 N0 M0 stage and a given indication for radical surgical resection to current S3-guidelines (this includes patients with a given indication for radical surgery after endoscopic-resection of a cT1-2 N0 M0 tumor [poor grading or L1/V1 invasion or basal R1 resection or deep submucosal infiltration]) (see section 4.2.3 for detailed information).
Patient has known hypersensitivity to any component of the durvalumab formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
Patient has any known contraindication (including hypersensitivity) to docetaxel, 5-FU, leucovorin (calcium folinate), or oxaliplatin. In cases of pernicious anemia or other anemias due to vitamin B 12 deficiency, folinic acid (Leucovorin) is contraindicated and trial inclusion is not possible or only possible after compensation the anaemic status.
Patient has a known dihydropyrimidine dehydrogenase (DPD) deficiency. Patients with reduced DPD activity (CPIC activity score of 1.0-1.5) might participate in the study and receive a reduced dosage of 5-FU.
Patient has active or history of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
Single group
Durvalumab
Drug1500 mg Durvalumab, IV, day 1 Q4W (max. 15 cycles)
FLOT
Drug50 mg/m² docetaxel, 85 mg/m² oxaliplatin, 200 mg/m² calcium folinate and 2600 mg/m² fluorouracil as 24 h-infusion, 2 cycles
mFOLFOX-6
Drug85 mg/m² oxaliplatin, 200 mg/m² calcium folinate, 400 mg/m² fluorouracil as bolus dose and 1600 mg/m² fluorouracil as 48 h-infusion, ² cycles
Radiotherapy
Radiation5 weeks with 5 days a week radiotherapy (25 daily fractions with 2.0 Gy = ∑50Gy)
Rate of clinical and pathological complete response (cCR/pCR)
Rate of clinical and pathological complete response rate at time of endoscopic re-evaluation (at the end of the core study treatment) according to Becker criteria and investigator-based RECIST v1.1 assessment as well as endoscopic response criteria similar to the Japanese Gastric Cancer Association Guideline
Rate of cCR/pCR (long term follow up)
Rate of cCR/pCR at 1, 2 and 3 years after start of treatment (long term follow up)
Subgroup analysis of cCR/pCR
Subgroup analysis of cCR/pCR rate at time of endoscopic re-evaluation and after 1 year according to following characteristics: MSI high, PD-L1 CPS\>1 and PD-L1 CPS\>5 and especially acc. to CPS ≥10 or \<10
Rate of salvage surgery
Rate of salvage surgery
Mortality
90-day as well as 1-year mortality after start of treatment in non-surgery population and population with salvage surgery
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