NCT06914011

Circulating Tumor DNA MRD-Guided Adjuvant Therapy for Curatively Resected Locally Advanced Esophageal Squamous Cell Carcinoma

Multi-center, Randomized, Phase III Trial of Circulating Tumor DNA MRD-Guided Adjuvant Therapy for Curatively Resected Locally Advanced Esophageal Squamous Cell Carcinoma (MRD2START)

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 172 (estimated)
• Sponsor: Asan Medical Center · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

This study was a multicenter, randomized, phase 3 trial to determine whether adjuvant chemotherapy including tisleliizumab improves recurrence-free survival compared to follow-up alone without chemotherapy in patients with curatively resected esophageal squamous cell carcinoma.

Detailed description

It aims to investigate the efficacy of adjuvant therapy in patients at high risk, as determined by the presence of MRD through cfDNA testing, following curative R0 resection for locally advanced esophageal squamous cell carcinoma. Patients found to be MRD-positive will be randomly allocated in a 2:1 ratio to either an adjuvant therapy arm or a surveillance arm. Randomization will be stratified based on the administration of pre-surgery neoadjuvant therapy (yes vs. no), the pathological stage after surgery (0-2 vs. 3-4), and institution. For participants assigned to the adjuvant therapy arm, those who underwent neoadjuvant chemoradiotherapy followed by surgery will receive adjuvant chemoimmunotherapy comprising paclitaxel + carboplatin + tislelizumab administered every 3 weeks for 4 cycles, followed by tislelizumab monotherapy every 6 weeks for 6 cycles. Patients who had upfront surgery without prior neoadjuvant therapy will receive adjuvant chemoradioimmunotherapy, starting with paclitaxel + carboplatin + tislelizumab every 3 weeks for one cycle, then concurrent radiotherapy (45 Gy in 25 fractions, 1.8 Gy/fraction) with paclitaxel + carboplatin + tislelizumab, followed by an additional cycle of paclitaxel + carboplatin + tislelizumab every three weeks, and concluding with tislelizumab monotherapy every 6 weeks for 6 cycles. MRD-negative patients are excluded from the phase 3 trial.

Conditions

• Esophageal Cancer

Interventions

Type	Name	Description
DRUG	Tislelizumab	* Participants who underwent upfront surgery without prior neoadjuvant therapy: * Tislelizumab 200 mg iv D1, Paclitaxel 175 mg/m2 iv D1, and Carboplatin AUC 5 mg/mL/min iv D1, in a 3-week cycle for one cycle * Concurrent radiotherapy (25 fractions of 1.8 Gy each, with 5 fractions per week) with Tislelizumab 200 mg iv D1, D22, Paclitaxel 50 mg/m2 iv D1, 8, 15, 22, 29, and Carboplatin AUC 2 mg/mL/min D1, 8, 15, 22, 29 * Tislelizumab 200 mg iv D1, Paclitaxel 175 mg/m2 iv D1, and Carboplatin AUC 5 mg/mL/min iv D1, in a 3-week cycle for 1 cycle * Tislelizumab 400 mg iv D1, in a 6-week cycle for six cycles * For participants who underwent neoadjuvant chemoradiotherapy followed by surgery will receive adjuvant chemoimmunotherapy in the following sequence: * Tislelizumab 200 mg iv D1, Paclitaxel 175 mg/m2 iv D1, and Carboplatin AUC 5 mg/mL/min iv D1, in a 3-week cycle for four cycles * Tislelizumab 400 mg iv D1, in a 6-week cycle for six cycles

Timeline

• Start date: 2026-01-06
• Primary completion: 2031-02-28
• Completion: 2034-05-30
• First posted: 2025-04-06
• Last updated: 2025-12-03