Chemoradiotherapy in Esophageal or Esophagogastric Junction Cancer

Study Overview
=================
Brief Summary
-----------------
Definitive chemoradiotherapy is the standard of care in unresectable esophageal or esophagogastric cancer. A multidisciplinary approach, including chemotherapy and radiotherapy, is important for these patients. Morerover, molecular targeting agents does not show clear efficacy in EC up to now. Nowadays, the pace of development of cancer immunotherapies is accelerating. Clinical evidence of the efficacy of immune checkpoint inhibitors and adoptive immunotherapies herald the onset of a new era in cancer immunotherapy. There have also been recent developments to provide a promising frontier in extending the use of immunotherpay or targeting agents to radiotherapy. The purpose of this study was to explore the optimal treatment modalities including PD-1/PD-L1 antibody or targeted drug for patients with unresectable esophageal or esophagogastric junction cancer.

Official Title
-----------------
Cohort Study of Definitive Chemoradiotherapy for Esophageal or Esophagogastric Junction Cancer

Conditions
-----------------
Esophagus Cancer, Esophagogastric Junction Cancer, Chemoradiation, Targeted Therapy, Immunotherapy, Chemotherapy Effect

Intervention / Treatment
-----------------
* Radiation: Radiotherapy
* Drug: Platinum based chemotherapy
* Drug: Paclitaxel based chemotherapy
* Drug: Immunotherapy
* Drug: 5-FU Analog based chemotherapy
* Drug: Nimotuzumab


Participation Criteria
=================
Eligibility Criteria
-----------------
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
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Definitive Chemoradiation<br>This arm received chemoradiation without immunotherapy/targeting agents as definitive treatment. | Radiation: Radiotherapy<br>* 50-66Gy/1.8-2.2Gy/25-30f<br>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>Drug: 5-FU Analog based chemotherapy<br>* W1-5 qW or d1-14, q3W according to physician's preference<br>|
| Experimental: Chemoradiation Combined With Immunotherapy/targeting agents<br>This arm received chemoradiation with immunotherapy/targeting agents as definitive treatment. | Radiation: Radiotherapy<br>* 50-66Gy/1.8-2.2Gy/25-30f<br>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>Drug: Immunotherapy<br>* Anti-PD-1/PD-L1 Antibody<br>Drug: 5-FU Analog based chemotherapy<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?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 1year | 
| Overall survival |  | 2 year | 
| Overall survival |  | 3 year | 
| 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 |  | 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 |