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

NCT ID: NCT04280822

Last Updated: 2022-10-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-21
• Study Completion Date: 2028-03-02

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.

Conditions

Esophageal Cancer; Surgery; Neoadjuvant Treatment; Survival

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Neoadjuvant immunochemotherapy

Intervention Type: DRUG

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

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).

Group Type: ACTIVE_COMPARATOR

Neoadjuvant immunochemotherapy

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: DRUG

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。

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Henan Cancer Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yan Zheng, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university

Locations

Henan Cancer Hospital (The Affiliated Cancer Hospital of Zhengzhou University)

Zhengzhou, Henan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yan Zheng, PhD, MD

Role: CONTACT

sunnyzheng1@126.com

+86+15713660065

Haibo Sun, PhD, MD

Role: CONTACT

sunny-haipo@hotmail.com

Facility Contacts

Yan Zheng, PhD

Role: primary

sunnyzheng1@126.com

86-371-65587226

References

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.

Reference Type: DERIVED

PMID: 33553366 (View on PubMed)

Other Identifiers

HCHTOG1909

Identifier Type: -

Identifier Source: org_study_id