Patient-reported Outcomes in Preoperative Immunochemotherapy/Radiotherapy-treated Esophageal Cancer Patients

Study Overview
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Brief Summary
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Preoperative Immune checkpoint inhibitors combined with chemotherapy have revolutionized the treatment landscape of locally advanced esophageal squamous cell carcinoma. However, there are still a significant proportion of patients who could not benefit from such treatment modality. Currently, no effective biomarkers were identified to stratify responders and non-responders. Early dynamic and persistent relief of dysphagia may act as a predictive biomarker to reflect the on-treatment anti-tumor activity. In this prospective study, we aimed to explore the feasibility of using patient-reported outcomes (PROs) to predict the pathological complete response of esophageal squamous cell carcinoma patients treated with neoadjuvant immunochemotherapy with or without short-term radiation as well as to assess the efficacy and safety of short-term radiotherapy in PROs-insensitive patients after one cycle of neoadjuvant immunochemotherapy.

Official Title
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Patient-reported Outcome-based Surveillance System Evaluating Safety and Efficacy of Preoperative Immunochemotherapy +/- Chemoradiation in Patients With Esophageal Squamous Cell Carcinoma - A Prospective, Explorative, Phase II Study

Conditions
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Esophageal Squamous Cell Carcinoma, Patient-reported Outcomes, Immunotherapy

Intervention / Treatment
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* Drug: Paclitaxel-albumin
* Drug: Cisplatin
* Drug: Carboplatin
* Drug: Tislelizumab
* Radiation: VMAT or IMRT
* Procedure: Esophagectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed esophageal squamous cell carcinoma Potentially resectable esophageal squamous cell carcinoma at first diagnosis (cT1-4aN1-2M0, cT3-T4aN0M0) Treatment-naive Expected life span > 6 months Aged 18 - 75 years old Adequate organ functions PS 0-2 Participants are fully informed about the whole study and are willing to sign the informed consent Exclusion Criteria: Previous history of thoracic surgery or radiation Cervical or multi-origin esophageal cancer Known or suspected experimental drug allergy Pregnant or lactating women Esophagomediastianl fistula Peripheral neuropathy Previous cancer history other than esophageal cancer Severe organ function deterioration that can not tolerate neoadjuvant therapy Previous autoimmune diseases diabetic history > 10 years interstitial pulmonary disease, non-infectious pulmonitis Active type B hepatitis Any other conditions that may affect patients' safety and compliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant immunochemotherapy +/- short-term radiotherapy<br>Tislelizumab + cisplatin/carboplatin + albumin-bounded paclitaxel +/- radiotherapy | Drug: Paclitaxel-albumin<br>* 260mg/m2, ivdrip, d1<br>Drug: Cisplatin<br>* 60mg/m2, ivdrip, d1<br>Drug: Carboplatin<br>* AUC=4-6, ivdrip, d1<br>Drug: Tislelizumab<br>* 200mg, ivdrip, d1<br>Radiation: VMAT or IMRT<br>* 15Gy/5F (d43-d50, d57-d64), 5 times a week<br>Procedure: Esophagectomy<br>* Minimally-invasive or open McKeown and Ivor-Lewis esophagectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete response rate | The rate of pathologic complete response rate after the combined treatment of chemotherapy and immunotherapy following surgery | Three to five working days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | iRECIST criteria defined complete response and partial response | Up to 24 weeks | 
| Safety as measured by number of participants with Grade 3 and 4 adverse events | Number of Grade 3 and 4 adverse events as defined by CTCAE v5.0 | Up to 12 weeks | 
| R0 resection rate R0 resection rate R0 resection rate R0 resection rate R0 resection rate R0 resction rate | The R0 resection rate of esophagectomy | Three to five working days after surgery | 
| Major pathological response | less than 10% residual viable tumor follow neoadjuvant therapy | Three to five working days after surgery | 
| Overall survival | Overall survival rate | From the date of diagnosis to the date of death, assessed up to 100 months | 
| Event-free survival | EFS | From the date of treatment initiation to the date of first progression (local recurrence of tumor or distant metastasis) or death from any cause, assessed up to 100 months | 
| Dysphagia relief score | DRS | score calculated by EORTC OES-18 dysphagia scale criteria at each cycle up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pathological complete response, Efficacy, Safety, Dysphagia