NCT05713838

Organ Preservation With Durvalumab-based Immunotherapy in Combination With Chemoradiation as Definitive Therapy for Early Stage Esophageal Adenocarcinoma With Indication for Radical Surgery

Organ Preservation With Durvalumab-based Immunotherapy in Combination With Chemoradiation as Definitive Therapy for Early Stage, cT1 and cT2N0, Esophageal Adenocarcinoma With Indication for Radical Surgery: A Prospective, Multicenter Study of the FLOT-AIO Gastric Cancer Group

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Patients with early stage, cT1 and cT2N0 esophageal adenocarcinoma with indication for radical surgery (esophagectomy or transhiatal extended gastrectomy) will be enrolled in two cohorts according to their PD-L1 CPS (cohort 1 CPS \< 10, cohort 2 CPS ≥ 10). All patients will receive core treatment consisting of immunotherapy with durvalumab in parallel to 2 cycles FLOT chemotherapy, followed by immunotherapy with durvalumab in parallel to 3 cycles of modified FOLFOX plus concomitant radiation (50 Gy). Eight weeks after this, patients will undergo tumor assessment consisting of esophagogastroduodenoscopy with extensive biopsies (bite-on-bite biopsies and fine-needle aspiration), endoscopic ultrasonography with measurement of maximum tumor thickness, and CT- or MRI-scans for tumor re-evaluation. Surgical resection would be offered only to those patients in whom a locoregional persistence is confirmed on tumor assessment, in the absence of any signs of distant dissemination. Patients with complete remission will enter the maintenance phase receiving durvalumab monotherapy for up to 12 cycles. The primary objective of this trial is to investigate the treatment efficacy of the combination of durvalumab and chemoradiation as organ preservative treatment option avoiding mortality and surgical complications with rate of clinical and pathological complete response (cCR/pCR) at time of endoscopic re-evaluation defined as primary efficacy endpoint. The secondary objectives are the further assessment of the efficacy of the combination of durvalumab and chemoradiation as organ preservative treatment option 1-/2- and 3-year cCR/pCR rate, rate of salvage surgery, 90-day and 1-year mortality as secondary endpoints and to assess the quality of life (QoL).

Conditions

• Esophagus Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Durvalumab	1500 mg Durvalumab, IV, day 1 Q4W (max. 15 cycles)
DRUG	FLOT	50 mg/m² docetaxel, 85 mg/m² oxaliplatin, 200 mg/m² calcium folinate and 2600 mg/m² fluorouracil as 24 h-infusion, 2 cycles
DRUG	mFOLFOX-6	85 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
RADIATION	Radiotherapy	5 weeks with 5 days a week radiotherapy (25 daily fractions with 2.0 Gy = ∑50Gy)

Timeline

• Start date: 2023-08-28
• Primary completion: 2025-12-01
• Completion: 2028-12-01
• First posted: 2023-02-06
• Last updated: 2024-09-19

Locations

22 sites across 1 country: Germany