Camrelizumab Plus Neoadjuvant Chemotherapy or Chemoradiotherapy Versus Chemoradiotherapy in Resectable ESCC.

Camrelizumab Plus Neoadjuvant Chemotherapy or Chemoradiotherapy Versus Neoadjuvant Chemoradiotherapy Alone for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma (NICE 2): a Multi-center, Randomized Phase II Trial

The purpose of this study is to explore the effectiveness and safety of neoadjuvant immune combined chemotherapy or radiochemotherapy compared with traditional neoadjuvant radiochemotherapy in patients with locally advanced Esophageal Squamous Cell Carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Resectable Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Camrelizumab; Radiation: radiotherapy

Detailed Description

This study aimed to evaluate the efficacy and safety of adding immunotherapy to neoadjuvant chemotherapy (CT) or chemoradiotherapy (CRT) compared to neoadjuvant CRT alone for resectable locally advanced esophageal squamous cell carcinoma (ESCC)

• Study Type: Interventional
• Enrollment (Estimated): 426
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yang Yang; Phone Number: 18930598090; Email: yangyang321879@163.com

Study Locations

• China
  • Anyang, China
    • Recruiting
    • Anyang Tumour Hospital
    • Contact: Weijie Wang
  • Guangzhou, China
    • Recruiting
    • Sun yat-sen University Cancer Center
    • Contact: Hong Yang
  • Hefei, China
    • Recruiting
    • Anhui Provincial Hospital
    • Contact: Xinyu Mei
  • Shanghai, China
    • Recruiting
    • Zhongshan Hospital of Fudan University
    • Contact: Lijie Tan
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Shanghai Chest Hospital
      • Principal Investigator: Zhigang Li
      • Contact: Yang Yang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The result of pathological biopsy showed esophageal squamous cell carcinoma;
2. Have not received systemic or local treatment for esophageal cancer in the past;
3. Age 18-75 years (including 18 and 75 years old), both male and female;
4. ECOG score 0-1;
5. Thoracic esophageal cancer assessed by CT/MRI/PET-CT etc. as resectable and the clinical stage is T1b-3N1-3M0 or T3N0M0, according to the 8th edition of AJCC staging;
6. Those who are expected to achieve R0 resection;
7. Voluntarily sign an informed consent form before treatment;
8. Plan to receive surgical treatment after neoadjuvant treatment is completed;
9. No surgical contraindications;
10. Normal function of major organs
11. Female subjects with fertility must undergo a serum pregnancy test within 72 hours before starting the study drug administration, and the result is negative, and take effective contraception during the trial and at least 3 months after the last administration Measures (such as intrauterine devices, contraceptives, or condoms); for male subjects whose partners are females of childbearing age, effective contraceptive measures should be taken during the trial and within 3 months after the last administration;
12. The subjects have good compliance and can follow up the efficacy and adverse events/reactions according to the requirements of the plan;

Exclusion Criteria:

1. There are unresectable factors, including unresectable tumors, unresectable contraindications for surgery, or rejection of surgery;
2. Patients with supraclavicular lymph node metastasis;
3. Poor nutritional status, BMI <18.5 Kg/m2; if the symptomatic nutritional support is corrected before randomization, the main investigator can continue to consider it after evaluation;
4. Those who are known to have a history of allergies to the drug components of this program;

5. Have received or are receiving any of the following treatments in the past:

   1. Any radiotherapy, chemotherapy or other anti-tumor drugs for tumors;
   2. Immunosuppressive drugs or systemic hormone drugs are being used within 2 weeks before the first use of the study drug to achieve immunosuppressive purposes (dose>10mg/day prednisone or equivalent dose); if there is no active autoimmune disease In the case of inhalation or topical use of steroids and prednisone doses> 10 mg/day or equivalent doses of adrenal cortex hormone replacement are allowed;
   3. Received a live attenuated vaccine within 4 weeks before using the study drug for the first time;
   4. Have undergone major surgery or severe trauma within 4 weeks before using the study drug for the first time;
6. A history of immunodeficiency, including a positive HIV test, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation;
7. There are clinical symptoms or diseases of the heart that are not well controlled;
8. Severe infections (CTCAE v5.0> level 2) occurred within 4 weeks before the first use of the study drug, such as severe pneumonia, bacteremia, infectious comorbidities that require hospitalization, etc.; baseline chest imaging examinations suggest activity Pulmonary inflammation, symptoms and signs of infection in the 14 days before the first use of the study drug, or those who require oral or intravenous antibiotic treatment, except for the prophylactic use of antibiotics;
9. Participated in other drug clinical studies within 4 weeks before randomization;
10. People who are currently accompanied by interstitial pneumonia or interstitial lung disease, or have a history of interstitial pneumonia or interstitial lung disease that requires hormone therapy, or have other pulmonary fibrosis that may interfere with the judgment and management of immune-related lung toxicity , Organizing pneumonia (such as bronchiolitis obliterans), pneumoconiosis, drug-related pneumonia, idiopathic pneumonia, or subjects whose CT shows active pneumonia or severe lung dysfunction during the screening period; active tuberculosis;
11. Patients with any active autoimmune diseases or history of autoimmune diseases with the possibility of recurrence; patients with skin diseases that do not require systemic treatment, such as leukoplakia, psoriasis, hair loss, and insulin treatment Patients with controllable type I diabetes or a history of asthma, but who have been completely relieved during childhood without any intervention can be included in the group; patients with asthma who need bronchodilator intervention cannot be included in the group;
12. There is active hepatitis B (HBV-DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody is positive, and HCV-RNA is higher than the lower limit of the analytical method);
13. Other malignant tumors have been diagnosed within 5 years before the first use of the study drug, unless malignant tumors with low risk of metastasis or death (5-year survival rate> 90%), such as fully treated skin basal cell carcinoma or squamous cell Skin cancer or cervical carcinoma in situ, etc., may be considered for inclusion;
14. Women who are pregnant or breastfeeding;
15. According to the judgment of the investigator, there are other factors that may lead to the forced termination of the study, such as suffering from other serious diseases (including mental illness) requiring combined treatment, alcoholism, drug abuse, family or social factors, which may affect the subjects Factors of safety or compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant Chemotherapy With Camrelizumab; Chemotherapy: Paclitaxel（Albumin Bound）100mg/m2, Day 1,8,15，Carboplatin AUC=5mg/ml/min, Day 1； Camrelizumab: Day 1, every 3 weeks, 2 cycles; Postoperative adjuvant treatment: Camrelizumab maintenance	Drug: Camrelizumab; The study perform preoperative neoadjuvant therapy, surgery and postoperative adjuvant therapy on subjects. Preoperative neoadjuvant therapy includes 3 groups: iCamrelizumab combined with neoadjuvant chemotherapy; Camrelizumab combined with neoadjuvant radiochemotherapy, and neoadjuvant radiochemotherapy.
Experimental: Neoadjuvant Radiochemotherapy With Camrelizumab; Chemotherapy: Paclitaxel 50mg/m2, Day 1,8,15,22,29，Carboplatin AUC=2mg/ml/min，Day 1,8,15,22,29 Camrelizumab: 200mg，Day 1,22 Radiotherapy: 41.4 Gy , D1-5/W Postoperative adjuvant treatment：Camrelizumab maintenance	Drug: Camrelizumab; The study perform preoperative neoadjuvant therapy, surgery and postoperative adjuvant therapy on subjects. Preoperative neoadjuvant therapy includes 3 groups: iCamrelizumab combined with neoadjuvant chemotherapy; Camrelizumab combined with neoadjuvant radiochemotherapy, and neoadjuvant radiochemotherapy.; Radiation: radiotherapy; The study perform preoperative neoadjuvant therapy, surgery and postoperative adjuvant therapy on subjects. Preoperative neoadjuvant therapy includes 3 groups: iCamrelizumab combined with neoadjuvant chemotherapy; Camrelizumab combined with neoadjuvant radiochemotherapy, and neoadjuvant radiochemotherapy.
Active Comparator: Neoadjuvant Radiochemotherapy; Chemotherapy: Paclitaxel 50mg/m2, Day 1,8,15,22,29，Carboplatin AUC=2mg/ml/min，Day 1,8,15,22,29 Radiotherapy：41.4 Gy , D1-5/W. Postoperative adjuvant treatment: non-pCR: Camrelizumab maintenance; PCR: surveillance	Radiation: radiotherapy; The study perform preoperative neoadjuvant therapy, surgery and postoperative adjuvant therapy on subjects. Preoperative neoadjuvant therapy includes 3 groups: iCamrelizumab combined with neoadjuvant chemotherapy; Camrelizumab combined with neoadjuvant radiochemotherapy, and neoadjuvant radiochemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFS assessed by the investigator according to RECIST 1.1	defined as event free survival,defined as the time from randomization to the occurrence of tumor progression/recurrence /death, whichever comes first	median EFS approximately over 45 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HRQoL	defined as quality and nutrition assessment	approximately 48 months
OS	defined as the time from registration to death due to any cause, or censored at date last known alive	median OS approximately over 80 months
R0 resection rate	defined as complete surgery resection rate	within 28 working days after surgery
DFS	defined as the time from the date of surgery who completed R0 resection to local or distant recurrence, or death due to any cause, whichever occurs first;	median DFS approximately over 40 months
pCR	pCR is defined as pathological complete response(ypT0/TisN0)	within 28 working days after surgery
MPR	MPR is defined as the percentage of subjects with <10% residual tumor in the primary tumor site	within 28 working days after surgery
Adverse events (AEs)	Incidence and grade (including serious adverse events [SAEs] and immune-related adverse events [irAEs]), determined according to the NCI-CTCAE 5.0 criteria	through study completion, assessed up to 50 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
biomarker testing	explore the correlation between the expression of PD-L1 and outcomes	approximately 48 months

Collaborators and Investigators

• Sponsor: Zhigang Li
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Yang Yang, Shanghai Chest Hospital

Publications and helpful links

General Publications

• Yang Y, Zhu L, Cheng Y, Liu Z, Cai X, Shao J, Zhang M, Liu J, Sun Y, Li Y, Yi J, Yu B, Jiang H, Chen H, Yang H, Tan L, Li Z. Three-arm phase II trial comparing camrelizumab plus chemotherapy versus camrelizumab plus chemoradiation versus chemoradiation as preoperative treatment for locally advanced esophageal squamous cell carcinoma (NICE-2 Study). BMC Cancer. 2022 May 6;22(1):506. doi: 10.1186/s12885-022-09573-6.

Helpful Links

• ClinicalTrials.gov Results Data Element Definitions for Interventional and Observational Studies (相关术语定义)
• Checklists, templates, and examples to help gather information needed to report results to ClinicalTrials.gov (试验结果填写指南)

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: September 5, 2021
• First Submitted That Met QC Criteria: September 5, 2021
• First Posted (Actual): September 14, 2021

Study Record Updates

• Last Update Posted (Actual): October 17, 2024
• Last Update Submitted That Met QC Criteria: October 14, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: LS2160

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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