Neoadjuvant Immunotherapy Plus CRT Versus Neoadjuvant CRT for Locally Advanced Resectable ESCC

NCT ID: NCT04973306

Last Updated: 2022-06-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 176 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-02
• Study Completion Date: 2027-07-31

Brief Summary

The purpose of this study was to evaluate the safety, feasibility and outcome of anti-PD-1 antibody (Tislelizumab, BeiGene) combined with neoadjuvant chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by minimally invasive esophagectomy for locally advanced resectable esophageal squamous cell carcinoma (cII-III Stage) patient.

Detailed Description

It is a prospective randomized phase II&III clinical trial sponsored by Shanghai Zhongshan Hospital with other twelve hospitals in China participating in. 476 patients with locally advanced resectable esophageal squamous cell carcinoma (cII-III Stage) are recruited and randomly assigned into the neoadjuvant chemoradiotherapy combined with immunotherapy group (nCRT plus anti-PD-1 Group) and the neoadjuvant chemoradiotherapy group (nCRT Group) according to the proportion of 1:1. The safety, efficacy of protocols and prognosis of patients are compared between the two regimens.

Conditions

Esophageal Squamous Cell Carcinoma Stage II; Esophageal Squamous Cell Carcinoma Stage III

Study Design

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

Study Groups

Neoadjuvant chemoradiotherapy combined with anti-PD-1 antibody

Neoadjuvant chemoradiotherapy (NCRT) combined with tislelizumab is performed followed by Ivor-Lewis or Mckeown esophagectomy in enrolled patients.

Group Type: EXPERIMENTAL

Neoadjuvant Chemoradiotherapy

Intervention Type: PROCEDURE

Chemotherapy: carboplatin (AUC 2 mg/mL per min) and paclitaxel (50 mg/m2 of body-surface area) were administered intravenously for five cycles, starting on days 1, 8, 15, 22, and 29. For each cycle, Carboplatin and paclitaxel were administered 30 minutes apart.

Radiotherapy: A total radiation dose of 41.4 Gy was given in 23 fractions of 1.8 Gy, 5 days per week (Radiotherapy was performed on the 2nd, 3rd, 4th, 5th, and 6th day in each cycle, and only 3 times in the 5th cycle)

Tislelizumab

Intervention Type: DRUG

Tislelizumab (200mg/time) was administered intravenously on the 1st and 22nd day.

The intravenous injection lasts about 30 minutes (micropump is recommended, intravenous bolus is prohibited, duration should be not less than 20 minutes and not more than 60 minutes);

Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended)

Intervention Type: PROCEDURE

After neoadjuvant therapy, patients in groups receive Ivor-Lewis or Mckeown Esophagectomy (Mckeown Esophagectomy recommended)

Neoadjuvant chemoradiotherapy

Neoadjuvant chemoradiotherapy (NCRT) is performed followed by Ivor-Lewis or Mckeown esophagectomy in enrolled patients.

Group Type: ACTIVE_COMPARATOR

Neoadjuvant Chemoradiotherapy

Intervention Type: PROCEDURE

Chemotherapy: carboplatin (AUC 2 mg/mL per min) and paclitaxel (50 mg/m2 of body-surface area) were administered intravenously for five cycles, starting on days 1, 8, 15, 22, and 29. For each cycle, Carboplatin and paclitaxel were administered 30 minutes apart.

Radiotherapy: A total radiation dose of 41.4 Gy was given in 23 fractions of 1.8 Gy, 5 days per week (Radiotherapy was performed on the 2nd, 3rd, 4th, 5th, and 6th day in each cycle, and only 3 times in the 5th cycle)

Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended)

Intervention Type: PROCEDURE

After neoadjuvant therapy, patients in groups receive Ivor-Lewis or Mckeown Esophagectomy (Mckeown Esophagectomy recommended)

Interventions

Neoadjuvant Chemoradiotherapy

Chemotherapy: carboplatin (AUC 2 mg/mL per min) and paclitaxel (50 mg/m2 of body-surface area) were administered intravenously for five cycles, starting on days 1, 8, 15, 22, and 29. For each cycle, Carboplatin and paclitaxel were administered 30 minutes apart.

Radiotherapy: A total radiation dose of 41.4 Gy was given in 23 fractions of 1.8 Gy, 5 days per week (Radiotherapy was performed on the 2nd, 3rd, 4th, 5th, and 6th day in each cycle, and only 3 times in the 5th cycle)

Intervention Type: PROCEDURE

Tislelizumab

Tislelizumab (200mg/time) was administered intravenously on the 1st and 22nd day.

The intravenous injection lasts about 30 minutes (micropump is recommended, intravenous bolus is prohibited, duration should be not less than 20 minutes and not more than 60 minutes);

Intervention Type: DRUG

Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended)

After neoadjuvant therapy, patients in groups receive Ivor-Lewis or Mckeown Esophagectomy (Mckeown Esophagectomy recommended)

Intervention Type: PROCEDURE

Other Intervention Names

anti-PD-1 antibody

Eligibility Criteria

Inclusion Criteria

1. Histologically-confirmed esophageal squamous cell carcinoma and whose tissue samples were taken before treatment;

2. Tumors of the esophagus are located in the thoracic cavity;

3. Pre-treatment stage as clinical II-III (AJCC/UICC 8th Edition)

4. Age is between 18 years and 75 years;

5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and expected survival time ≥12 months;

6. Adequate cardiac function. All patients should perform ECG, and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction > 50 %;

7. Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in pulmonary function tests ;

8. Adequate bone marrow function (White Blood Cells >4x10^9 /L; Neutrophil >2.0×10^9 /L; Hemoglobin > 90 g/L; platelets>100x10^9 /L);

9. Adequate liver function (Total bilirubin <1.5x Upper Level of Normal (ULN); Aspartate transaminase(AST) and Alanine transaminase (ALT) <1.5x ULN);

10. Adequate renal function (Glomerular filtration rate (CCr) >60 ml/min; serum creatinine (SCr) ≤120 µmol/L);

11. The patient has provided written informed consent and is able to understand and comply with the study;

Exclusion Criteria

1. Patients with histological non-squamous cell carcinoma;

2. Patients with advanced non-operable or metastatic esophageal cancer;

3. Pre-treatment stage as cM+, cN3 or cT4b(non-curatively-resectable verified by the local surgical investigator, AJCC/UICC 8th Edition) or cTis-1a, cT1bN0;

4. Patients with another previous or current malignant disease which is likely to interfere with treatment or the assessment of response in the judgement of the local surgical investigator;

5. Patients who have received or are receiving other chemotherapy, radiotherapy or targeted therapy;

6. Patients with autoimmune diseases history;

7. Recently or currently taking Glucocorticoids or Immunosuppressants;

8. Patients who underwent immunotherapy in the past;

9. Allergy to any antibody drugs or allergy to Paclitaxel and Carboplatin.

10. Past or currently suffering from chronic or recurrent autoimmune diseases;

11. Patients with active infection of immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); HIV seropositivity; HBV DNA or HCV RNA positive;

12. Patients with organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation);

13. Patients with severe systematic intercurrent disease, such as active infection or poorly controlled diabetes; coagulation disorders; hemorrhagic tendency or under treatment of thrombolysis or anticoagulant therapy;

14. Any patient with a significant medical condition which is thought unlikely to tolerate the therapies. Such as cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months), clinically-significant lung disease, clinically-significant bone marrow, liver, renal function disorder;

15. Pregnant or lactating women and fertile women who will not be using contraception during the trial;

16. Participation in another intervention clinical trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention during this study or during the last 30 days prior to informed consent;

17. Expected lack of compliance with the protocol.

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

Sponsors

Peking University Cancer Hospital & Institute

OTHER

Sponsor Role: collaborator

Shanghai Chest Hospital

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: collaborator

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: collaborator

Ningbo Medical Center Lihuili Hospital

OTHER_GOV

Sponsor Role: collaborator

The First People's Hospital of Changzhou

OTHER

Sponsor Role: collaborator

Zhongshan Hospital (Xiamen), Fudan University

OTHER

Sponsor Role: collaborator

Xuhui Central Hospital, Shanghai

OTHER

Sponsor Role: collaborator

Shanghai Minhang Central Hospital

OTHER

Sponsor Role: collaborator

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Zhejiang Cancer Hospital

OTHER

Sponsor Role: collaborator

Sichuan Cancer Hospital and Research Institute

OTHER

Sponsor Role: collaborator

Tongji Hospital

OTHER

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: collaborator

Shanghai Fifth People's Hospital

UNKNOWN

Sponsor Role: collaborator

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lijie Tan, MD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Zhongshan Hospital

Locations

Shanghai Zhongshan Hospital

Shanghai, , China

Site Status: RECRUITING

Countries

China

Facility Contacts

Lijie Tan, MD

Role: primary

tan.lijie@zs-hospital.sh.cn

+8621-64041990-692017

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Other Identifiers

B2021-369R

Identifier Type: -

Identifier Source: org_study_id