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

Phase 3

Recruiting

• Conditions: Esophageal Cancer; Surgery; Neoadjuvant Treatment; Survival
• Interventions: Drug: Neoadjuvant immunochemotherapy

• Registration Number: NCT04280822
• Lead Sponsor: Henan Cancer Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2020-02-18
• Study First Submitted QC: 2020-02-20
• Study First Posted: 2020-02-21
• Study Start: 2020-04-21
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-02
• Last Update Posted: 2022-10-04
• Primary Completion: 2023-12-02
• Study Completion: 2028-03-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 400

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Neoadjuvant immunochemotherapy	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)
Neoadjuvant chemotherapy	Neoadjuvant immunochemotherapy	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).

Primary Outcome Measures

Name	Time	Method
Event-free survival (EFS)	The date from the beginning of randomization to the date of first record. 5 years 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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Henan Cancer Hospital (The Affiliated Cancer Hospital of Zhengzhou University); 🇨🇳 Zhengzhou, Henan, China