Neoadjuvant Treatment Modalities in Esophageal Cancer

Study Overview
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Brief Summary
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Esophageal cancer is the most prevalent cancer globally with poor survival outcome. The prognosis with surgery alone is poor, accounting for 30-40% of overall survival at 5 year. Either neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) has been shown as efficatious therapy to improve patients outcomes in esophageal or esophagogastric junction cancer as compared with surgery alone. The purpose of this study was to explore the optimal neoadjuvant treatment modalities including PD-1/PD-L1 antibody or targeted drug for patients with esophageal or esophagogastric junction cancer.

Official Title
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Cohort Study of Neoadjuvant Treatment Modalities for Esophageal Cancer

Conditions
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Esophageal Cancer, Chemotherapy Effect, Chemoradiation, Surgery, Targeted Therapy, Immunotherapy, Esophagogastric Juction Cancer

Intervention / Treatment
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* Drug: Platinum based chemotherapy
* Drug: Paclitaxel based chemotherapy
* Radiation: Radiotherpay
* Procedure: Surgery
* Drug: Immunotherapy
* Drug: 5-FU Analog based chemotherpay
* Drug: Nimotuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years； Esophageal or Esophagogastric cancer； Histologically proven squamous cell carcinoma or adenocarcinoma in patients staged as I-IVa (AJCC 8th)； Primary treatment performed in Cancer Hospital, Chinese Academy of Medical Sciences； ECOG PS score: 0 1； Estimated survival time ≥3 months； Normal organ and marrow function as defined below:Hemoglobin: greater than or equal to 100g/L ;Leukocytes: greater than or equal to 4,000 G/L; Neutrophil: greater than or equal to 2,000 G/L; Platelets: greater than or equal to 100,000/mm3 ; Creatinine: less than or equal to 1.5 times the upper limit or CCR greater than or equal to 60 ml/min; AST/ALT: less than or equal to 2.5 times the upper limit; Total bilirubin: less than or equal to 1.5 times the upper limit; INR: less than or equal to 1.5 times the upper limit; APTT: less than or equal to 1.5 times the upper limit; PT: less than or equal to 1.5 times the upper limit； Informed consent； Exclusion Criteria: With any distant metastasis out of regional lymphatic drainage or in liver, lung, bone, CNS, etc； Patients with other cancer history in 5 years except cervical carcinoma in situ and non-malignant melanoma skin cancer； Existing active infection such as active tuberculosis and hepatitis； History of myocardial infarction within the past 6 months or history of ventricular arrhythmia； Uncontrolled illness including, but not limited to, active infection, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness History of allergic reactions attributed to paclitaxel, albumin or cisplatin； Participation in other clinical trials currently or within 4 weeks of selection； Pregnant or lactating females； Absence of medical records.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: (Neoadjuvant chemotherapy) nCT<br>This arm received chemotherapy with or without immunotherapy/targeting agents as neoadjuvant treatment. | Drug: Platinum based chemotherapy<br>* q1-3W according to physician's preference<br>Drug: Paclitaxel based chemotherapy<br>* q1-3W according to physician's preference<br>Radiation: Radiotherpay<br>* 40-50Gy/1.8-2.2Gy/20-25f<br>Procedure: Surgery<br>* Radical esophagectomy<br>Drug: Immunotherapy<br>* Anti-PD-1/PD-L1 Antibody<br>Drug: 5-FU Analog based chemotherpay<br>* W1-5 qW or d1-14, q3W according to physician's preference<br>Drug: Nimotuzumab<br>* 200-400mg, d1,qW<br>|
| Placebo Comparator: (Neoadjuvant Chemoradiation) nCRT<br>This arm received chemoradiotherapy with or without immunotherapy/targeting agents as neoadjuvant treatment. | Drug: Platinum based chemotherapy<br>* q1-3W according to physician's preference<br>Drug: Paclitaxel based chemotherapy<br>* q1-3W according to physician's preference<br>Procedure: Surgery<br>* Radical esophagectomy<br>Drug: Immunotherapy<br>* Anti-PD-1/PD-L1 Antibody<br>Drug: 5-FU Analog based chemotherpay<br>* W1-5 qW or d1-14, q3W according to physician's preference<br>Drug: Nimotuzumab<br>* 200-400mg, d1,qW<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | 1 year, 2 year, 3 year, 5 year | 
| Number of participants with Acute and late toxicities of radiotherapy,chemotherapy and immunotherapy | Acute and late toxicities are evaluated by NCI-CTC version 5.0 | 3 months | 
| Pathological response rate | Pathological response were classiﬁed into three grades.Grade I signiﬁes that there is little shrinkage in the tumor; only mild regression in the tumor cells is observed under themicroscope. Grade II shows gross reduction in size of the tumor and marked regression in the cancer cells microscopically, yet viable nests of cancer tissue are still visible. Grade III implies complete or almost total resolution of the tumor on exploration, and disappearance of the tumor tissue microscopically; only remnants of degenerated cancer cells can be seen (so-called ghost cancer cells). | 3 months | 
| R0 resection rate |  | 3 months | 
| Locoregional recurrence free survival |  | 1 year, 2 year, 3 year, 5 year | 
| Distant metastasis free survival |  | 1 year, 2 year, 3 year, 5 year |