121TiP - Prospective, single arm, phase II clinical trial of pembrolizumab combined with neoadjuvant chemoradiotherapy and surgery for locally advanced upper esophageal squamous cell carcinoma

Background

Definitive chemoradiotherapy (dCRT) is recommended as the standard treatment for locally advanced cervical esophageal cancer (EC). However, the recurrence rate of cervical or upper thoracic EC patients (pts) who only received high-dose dCRT was still as high as about 60% within 3 years, and the 5-year survival rate was about 30%. Therefore, these pts need more effective treatment to prevent recurrence and prolong survival.

Trial Design

The study is a prospective, single center, single arm phase II trial, aims to explore the safety and feasibility of pembrolizumab (Pem) combined with neoadjuvant chemoradiotherapy and surgery for locally advanced upper esophageal squamous cell carcinoma (ESCC). Pts are eligible with cT1-3N1-2M0 or cT2-3N0M0 (according to UICC/AJCC 8^th and JES) high (the distance from the upper edge of the tumor to the esophageal entrance ≤ 5cm) ESCC. 5 subjects are first enrolled as safety run-in part. After comprehensive risk assessment, continued to include 40 subjects. The subjects first received the 2 cycles of induction treatment (Pem 200mg, IV, D1, q3w +albumin paclitaxel, 125mg/m², IV, D1/D8, q3w +cisplatin, 70mg/m² in total, IV, given in three times, q3w) for 6 weeks, then received the sequential treatment (Pem 200mg, IV, D1, q3w, 2 cycles +albumin paclitaxel, 100mg, IV, D1, QW, 4 cycles+ cisplatin, 20mg/m², IV, D1, QW, 4 cycles + PTV, 44gy/2gy/22fx, 5 days a week, 5 weeks in total) for 6 weeks, and then received surgery with 4-8 weeks. For pts with non-pCR after surgery, continue to receive maintenance therapy of Pem after surgery (until 1 year or disease progression or intolerable toxicity); Follow up for pts with pCR. Safety follow-up will be conducted after the first medication or within 30 days after surgery (whichever occurs first). The primary endpoint is major pathological response, which is defined as ≤ 10% of residual viable tumor at the time of resection.

Clinical trial identification

NCT05541445.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.