Clinical trial NCT05043688: Camrelizumab Plus Neoadjuvant Chemotherapy or Chemoradiotherapy Versus Chemoradiotherapy in Resectable ESCC.
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Resectable Esophageal Squamous Cell Carcinoma
Lead sponsor: Shanghai Chest Hospital
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2021-09-14
Enrollment: 426
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 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.

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)

Eligibility criteria: 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.

Primary outcomes:
measure: EFS assessed by the investigator according to RECIST 1.1
timeFrame: median EFS approximately over 45 months
Secondary outcomes:
measure: OS
timeFrame: median OS approximately over 80 months
measure: R0 resection rate
timeFrame: within 28 working days after surgery
measure: DFS
timeFrame: median DFS approximately over 40 months
measure: HRQoL
timeFrame: approximately 48 months
measure: pCR
timeFrame: within 28 working days after surgery
measure: MPR
timeFrame: within 28 working days after surgery
measure: Adverse events (AEs)
timeFrame: through study completion, assessed up to 50 months
Other outcomes:
measure: biomarker testing
timeFrame: approximately 48 months
Locations:
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
city: Anyang
country: China
facility: Anyang Tumour Hospital
city: Guangzhou
country: China
facility: Sun yat-sen University Cancer Center
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital of Fudan University
Study officials:
affiliation: Shanghai Chest Hospital
name: Yang Yang
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.