Clinical trial NCT04280822: Neo-adjuvant Immunochemotheray Versus Neo-adjuvant Chemotherapy for Resectable Esophageal Carcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Esophageal Cancer
Surgery
Neoadjuvant Treatment
Survival
Keywords: Neoadjuvant chemotherapy
Neoadjuvant immunochemotherapy
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2020-02-21
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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。

Primary outcomes:
measure: Event-free survival (EFS)
timeFrame: The date from the beginning of randomization to the date of first record. 3 years EFS
measure: Event-free survival (EFS)
timeFrame: The date from the beginning of randomization to the date of first record. 5 years EFS
Secondary outcomes:
measure: pCR
timeFrame: within 14 working days after operation
measure: DFS
timeFrame: 3 years DFS
measure: DFS
timeFrame: 5 years DFS
measure: OS
timeFrame: 3 years OS
measure: OS
timeFrame: 5 years OS
measure: ORR
timeFrame: 3-4 weeks after the last cycle of neoadjuvant treatment
measure: R0 resection rate
timeFrame: within 14 working days after operation
measure: MPR
timeFrame: within 14 working days after operation
measure: EORTC QLQ-C30
timeFrame: before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation
measure: EORTC QLQ-OES18
timeFrame: before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation
measure: NRS-2002
timeFrame: before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Cancer Hospital (The Affiliated Cancer Hospital of Zhengzhou University)
state: Henan
Study officials:
affiliation: Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university
name: Yan Zheng, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.