Clinical trial NCT04973306: Neoadjuvant Immunotherapy Plus CRT Versus Neoadjuvant CRT for Locally Advanced Resectable ESCC
Official title: Neoadjuvant Immunotherapy Combined With Chemoradiotherapy Versus Neoadjuvant Chemoradiotherapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma (cII-III Stage): A Multi-center Prospective Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Esophageal Squamous Cell Carcinoma Stage II
Esophageal Squamous Cell Carcinoma Stage III
Keywords: Esophageal Squamous Cell Carcinoma
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
Collaborators: name: Peking University Cancer Hospital & Institute
name: Shanghai Chest Hospital
name: First Affiliated Hospital of Wenzhou Medical University
name: Tianjin Medical University Cancer Institute and Hospital
name: Ningbo Medical Center Lihuili Hospital
name: The First People's Hospital of Changzhou
name: Zhongshan Hospital (Xiamen), Fudan University
name: Xuhui Central Hospital, Shanghai
name: Shanghai Minhang Central Hospital
name: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Zhejiang Cancer Hospital
name: Sichuan Cancer Hospital and Research Institute
name: Tongji Hospital
name: Sun Yat-sen University
name: Shanghai Fifth People's Hospital
First posted: 2021-07-22
Enrollment: 176
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 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.

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:

Exclusion Criteria associated with Cancer:

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;

   Other Exclusion Criteria:
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.

Primary outcomes:
measure: Pathological response rate(pCR)
timeFrame: Up to the date of pathological reports obtained since the date of randomization, up to 12 months
measure: Overall survival(OS)
timeFrame: Up to the date of death of any causes since the date of randomization, up to 36 months
Secondary outcomes:
measure: Treatment related complications
timeFrame: Up to 1 month after surgery since the data of randomization, up to 13 months
measure: Progression-free survival(PFS)
timeFrame: Up to the date of disease recurrence since the date of randomization, up to 36 months
measure: R0 resection rate
timeFrame: Up to the date of pathological reports obtained since the date of randomization, up to 12 months
measure: Number and Location of positive lymph nodes
timeFrame: Up to the date of pathological reports obtained since the date of randomization, up to 12 months
measure: Overall Quality of life
timeFrame: Up to the end of follow-up since the data of surgery, up to 36 months
measure: Quality of life in eating and swallowing function
timeFrame: Up to the end of follow-up since the data of surgery, up to 36 months
measure: Recurrence-free survival (RFS)
timeFrame: Up to the date of disease recurrence since the date of surgery, up to 36 months
measure: Correlation between genetic profile and tumor response
timeFrame: Up to the end of follow-up since the data of surgery, up to 36 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Lijie Tan, MD
role: PRINCIPAL_INVESTIGATOR
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