NCT07507968

TNT With FLOT/Durvalumab Plus Post-OP Durvalumab for Resectable Gastroesophageal Adenocarcinoma

Total Neoadjuvant Treatment With Preoperative FLOT/Durvalumab Plus Postoperative Durvalumab for Resectable Gastroesophageal Adenocarcinoma

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 101 (estimated)
• Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This trial is designed to evaluate a total neoadjuvant approach using D-FLOT as the new standard backbone in patients with resectable esophagogastric adenocarcinoma. It addresses major limitations of current treatment paradigms, builds directly on the strong clinical signal from the MATTERHORN trial, and offers a rational, biologically sound framework for future therapy intensification and innovation. By moving systemic therapy entirely into the preoperative phase, we aim to: * Improve patient outcomes through better adherence and deeper response * Minimize postoperative therapy-related dropout * Create a platform for rational post-surgical drug testing and individualized treatment escalation The trial will provide pivotal evidence to guide the next generation of curative-intent treatment strategies for EGA.

Detailed description

The present clinical trial is a prospective, investigator-initiated, single-arm, open-label, multicenter, multi-national phase II trial. Patients with locally advanced, cT2-4 (any cN, M0) or any cT (cN+, M0), gastric, esophagogastric junction (type 1-3) or lower esophageal adenocarcinoma which are considered medically and technically resectable are eligible and will undergo baseline assessment. All patients will receive treatment consisting of up to eight 2-week cycles of FLOT chemotherapy (docetaxel 50 mg/m² IV, oxaliplatin 85 mg/m² IV, folinic acid 200 mg/m² IV, 5-FU 2,600 mg/m² IV; given on day 1 of each 2-weeks cycle \[Q2W\]) in combination with up to four 4-week cycles immunotherapy with durvalumab (1,500 mg IV, given on day 1 of each 4-weeks cycle \[Q4W\]). Four to eight weeks after last dose of preoperative treatment, patients will undergo surgical resection (tailored to the individual patient, according to local standards). Afterwards, patients will enter the maintenance phase receiving durvalumab monotherapy (1,500 mg IV, Q4W) for up to 10 cycles.

Conditions

• Esophagogastric Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Durvalumab	In the preoperative treatment phase, patients will receive eight 2-week cycles of FLOT chemotherapy (docetaxel 50 mg/m² IV, oxaliplatin 85 mg/m² IV, folinic acid 200 mg/m² IV, 5-FU 2,600 mg/m² IV; given on day 1 of each 2-weeks cycle \[Q2W\]). In addition, they will receive up to 4 treatments of durvalumab (1,500 mg) administrated by infusion on the first day of every second two-week cycle (Q4W). Four to eight weeks after the last dose of preoperative treatment, patients will undergo surgical resection. Study specifications for surgical resection are consistent with national guidelines. Surgical approaches will be tailored to the individual patient according to local standards with the goal of achieving R0-resection of the primary tumor. Four to twelve weeks after surgery, patients will receive durvalumab (1,500 mg IV, Q4W) monotherapy for a maximum of 10 cycles (14 cycles of durvalumab in total).

Timeline

• Start date: 2026-07-01
• Primary completion: 2030-02-01
• Completion: 2030-02-01
• First posted: 2026-04-02
• Last updated: 2026-04-02

Locations

29 sites across 2 countries: Germany, Spain