Neo-adjuvant Immunochemotheray Versus Neo-adjuvant Chemotherapy for Resectable Esophageal Carcinoma

A Phase III, Randomized Controlled Study of Neo-adjuvant Toripalimab (JS001) in Combination With Chemotherapy Versus Neo-adjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma

The effect of neo-adjuvant immunochemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas remains unknown. One of our objectives is to evaluate whether the neo-adjuvant immunochemotherapy Toripalimab (JS001) with cisplatin and paclitaxel followed by right thoracic approach esophagectomy with total 2-field lymph node dissection improves the overall survival of thoracic esophageal cancer patients versus neo-adjuvant chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer; Surgery; Survival; Neoadjuvant Treatment
• Intervention / Treatment: Drug: Neoadjuvant immunochemotherapy

Detailed Description

The effect of immunochemotherapy in second line treatment of esophageal cancer got a positive results in the world. We tried to apply the immunotheray in resectable esophageal cancer and have planed this phase III clinical trials. The optimal management of resectable esophageal squamous cell carcinomas may have a new chapter in the era of immunotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yan Zheng, PhD, MD; Phone Number: +86+15713660065; Email: sunnyzheng1@126.com
• Study Contact Backup: Name: Haibo Sun, PhD, MD; Email: sunny-haipo@hotmail.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Recruiting
      • Henan Cancer Hospital (The Affiliated Cancer Hospital of Zhengzhou University)
      • Contact: Yan Zheng, PhD; Phone Number: 86-371-65587226; Email: sunnyzheng1@126.com
      • Principal Investigator: Yan Zheng, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologic diagnosis of local advance squamous cell thoracic esophageal carcinoma of Stage (T1N1-3 or T2-3N0-3 M0), (8th Union for International Cancer Control, UICC-TNM).
2. No metastatic lymph node in cervical by color doppler sonography.
3. Patients must not have received any prior anticancer therapy of esophageal carcinoma.
4. Age ranges from 18 to 75 years.
5. Without operative contraindication.
6. Absolute white blood cells count ≥4.0×109/L, neutrophil ≥1.5×109/L, platelets ≥100.0×109/L, hemoglobin ≥90g/L, and normal functions of liver and kidney, total bilirubin（TBIL）≤1.5N, aspartate aminotransferase (AST)≤2.5N, alanine aminotransferase(ALT)≤2.5N, prothrombin time(PT)≤1.5N, and activated partial thromboplastin time(APTT) is in normal range, endogenous creatinine clearance rate(CRE)≤1.5N.
7. Patients must not have diagnosed with other cancer and must not received any prior anticancer therapy except prostatic cancer with more than 5 years disease-free survival(DFS).
8. expected R0 resection.
9. ECOG 0～1.
10. Patients should agree to use contraceptive measures during the study period and within 6 months of the end of the study. Women must be non-lactation.
11. Signed informed consent document on file. 10. .

Exclusion Criteria:

• 1. Multiple primary cancer. 2.Patients with infections disease that require treatment 3.Patients who need continuous hormone treatment 4.unstable angina within 3 months, myocardial infarction within 6 months 5.psychopath 6.Patients with concomitant hemorrhagic disease. 7.Any unexpected reason for patients can't get operation 8.Inability to use gastric conduit after esophagectomy because of a prior surgery.

  9.Pregnant or breast feeding 10.Patients are diagnosed or suspected to be allergic to cisplatin or Paclitaxel.

  11.Bronchial asthma who requires intermittent use of bronchodilators or medical interventions 12.Due to co-existing diseases, the immunosuppressant was used. And the dosage of immunosuppressant was more than 10mg/ day orally and more than 2 weeks before enrollment 13.Abnormal coagulation function (PT>16s, APTT>53s, TT>21s, Fib<1.5g/L), tendency of bleeding or receiving thrombolysis or anticoagulant therapy 14.Previous or present pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, lung function severely impaired 15.Autoimmune diseases, immune deficiency, organ transplantation； 16.Hepatitis b/c patients。

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Neoadjuvant immunochemotherapy; Neo-adjuvant chemotherapy(cisplatin and paclitaxel): Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles. JS001, 240mg ivgtt, d3, >30min, 3week, 2 cycles Surgery: 2-3weeks after Neo-adjuvant chemotherapy Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality. Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included). After surgery/ maintain period: JS001, 240mg ivgtt, d3, >30min, 3week (8 cycles at most)	Drug: Neoadjuvant immunochemotherapy; Neo-adjuvant chemotherapy(cisplatin and paclitaxel): Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles. JS001, 240mg ivgtt, d3, >30min, 3week, 2 cycles Surgery: 2-3weeks after Neo-adjuvant chemotherapy Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality. Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included). After surgery/ maintain period: JS001, 240mg ivgtt, d3, >30min, 3week (8 cycles at most)
ACTIVE_COMPARATOR: Neoadjuvant chemotherapy; Neo-adjuvant chemotherapy(cisplatin and paclitaxel): Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles. Surgery: 2-3weeks after Neo-adjuvant chemotherapy Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality. Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included).	Drug: Neoadjuvant immunochemotherapy; Neo-adjuvant chemotherapy(cisplatin and paclitaxel): Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles. JS001, 240mg ivgtt, d3, >30min, 3week, 2 cycles Surgery: 2-3weeks after Neo-adjuvant chemotherapy Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality. Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included). After surgery/ maintain period: JS001, 240mg ivgtt, d3, >30min, 3week (8 cycles at most)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	The date from the beginning of randomization to the date of first record of unresectable disease, distant metastases, local recurrences of any causes, and death of any cause.	The date from the beginning of randomization to the date of first record. 3 years EFS
Event-free survival (EFS)	The date from the beginning of randomization to the date of first record of unresectable disease, distant metastases, local recurrences of any causes, and death of any cause.	The date from the beginning of randomization to the date of first record. 5 years EFS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	pathological complete response rate	within 14 working days after operation
DFS	Disease free survival	3 years DFS
DFS	Disease free survival	5 years DFS
OS	Overall survival rate	3 years OS
OS	Overall survival rate	5 years OS
ORR	The Overall Response Rate. ORR=CR+PR. Criteria: Response Evaluation Criteria in Solid Tumors, RECIST.	3-4 weeks after the last cycle of neoadjuvant treatment
R0 resection rate	the complete resection rate of all tumor under microscope	within 14 working days after operation
MPR	MPR rate was defined as the percentage of patients who achieved a major pathological response (residual tumor ≤10%)	within 14 working days after operation
EORTC QLQ-C30	EORTC QLQ-C30 repeated measurement model	before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation
EORTC QLQ-OES18	EORTC QLQ-OES18 repeated measurement model	before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation
NRS-2002	NRS-2002 repeated measurement model	before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital

Publications and helpful links

General Publications

• Zheng Y, Liu XB, Sun HB, Xu J, Shen S, Ba YF, Yan M, Qin Z, Liu BX, Wang ZF, Liu SL, Zhang RX, Chen PN, Liang GH, Yuan D, Li ZX, Liu Q, Wang HR, Li HM, Lv H, Ma X, Zhu J, Yu YK, Xing WQ; written on Henan Cancer Hospital Thoracic Oncology Group (HCHTOG). A phase III study on neoadjuvant chemotherapy versus neoadjuvant toripalimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: Henan Cancer Hospital Thoracic Oncology Group 1909 (HCHTOG1909). Ann Transl Med. 2021 Jan;9(1):73. doi: 10.21037/atm-20-5404.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 21, 2020
• Primary Completion (ANTICIPATED): December 2, 2023
• Study Completion (ANTICIPATED): March 2, 2028

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 20, 2020
• First Posted (ACTUAL): February 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 4, 2022
• Last Update Submitted That Met QC Criteria: October 2, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Neoadjuvant chemotherapy; Neoadjuvant immunochemotherapy
• Other Study ID Numbers: HCHTOG1909

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No