NCT05740995

Neoadjuvant Anti-PD-1 Plus Chemotherapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma

A Single-center, Prospective Cohort Study of Neoadjuvant Anti-PD-1 Plus Chemotherapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 40 (estimated)
• Sponsor: Shanghai Zhongshan Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the outcomes and identify predictors of neoadjuvant anti-PD-1 plus chemotherapy in locally advanced resectable esophageal squamous cell carcinoma (ESCC). In this single-center cohort study, we are aiming to (1) evaluate the therapeutic efficacy and survival benefits on patients with locally advanced resectable ESCC (cT3-4aN0-1M0); (2) evaluate the value of genomic indicators including MMR alternation status in predicting therapeutic responses and prognosis; (3) evaluate the value of transcriptomic indicators including B cell lineage features in predicting therapeutic responses and prognosis; (4) evaluate the value of microbial and metabolite indicators in predicting therapeutic responses and prognosis. Whole exome sequencing, RNA sequencing, 16S rRNA sequencing and Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) of samples of patients to neoadjuvant chemoimmunotherapy before and after treatment are performed to explore the mechanisms of drug resistance and identification of predictive and prognosis biomarkers.

Detailed description

Multiple clinical trials investigated the safety and feasibility of neoadjuvant anti-PD-1 plus chemotherapy in esophageal squamous cell carcinoma (ESCC). However, the efficacy of neoadjuvant chemoimmunotherapy was undetermined and existing biomarkers failed to provide stable prediction of therapeutic responses. This study seek to further evaluate the clinical outcomes and identify biological predictors of neoadjuvant anti-PD-1 plus chemotherapy in locally advanced resectable esophageal squamous cell carcinoma (ESCC). In this single-center cohort study, our aims include: 1. evaluate the therapeutic efficacy and survival benefits on patients with locally advanced resectable ESCC (cT3-4aN0-1M0); 2. evaluate the value of genomic indicators in predicting therapeutic responses and prognosis; 3. evaluate the value of transcriptomic indicators in predicting therapeutic responses and prognosis; 4. evaluate the value of microbial and metabolite indicators in predicting therapeutic responses and prognosis. Whole exome sequencing, RNA sequencing, 16S rRNA sequencing and Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) of samples of responders and non-responders to neoadjuvant chemoimmunotherapy before and after treatment are performed to explore the mechanisms of drug resistance and identification of predictive and prognosis biomarkers, providing guidance to clinical decisions.

Conditions

• Esophageal Squamous Cell Carcinoma
• Neoadjuvant Chemoimmunotherapy

Interventions

Type	Name	Description
DRUG	neoadjuvant anti-PD-1 plus chemotherapy	Patients will be given preoperative treatment as below once recruited: 1. Chemotherapy is delivered and composed of two cycles of Nab-paclitaxel 135mg per square meter of body-surface area and cisplatin 75mg per square meter of body-surface area every 3 weeks; 2. PD-1 antibody is delivered 200 mg (iv, in 30 minutes) every 3 weeks; 3. After neoadjuvant therapy of 3-4 cycles, esophagectomy is performed. We advise starting 4 cycles of identical chemoimmunotherapy in 6w after surgery.

Timeline

• Start date: 2020-12-01
• Primary completion: 2023-12-01
• Completion: 2028-12-01
• First posted: 2023-02-23
• Last updated: 2023-03-21

Locations

1 site across 1 country: China