Neoadjuvant Immunotherapy Plus CRT Versus Neoadjuvant CRT for Locally Advanced Resectable ESCC
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
Shanghai Zhongshan Hospital
176 participants
Mar 2, 2022
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria11
- Histologically-confirmed esophageal squamous cell carcinoma and whose tissue samples were taken before treatment;
- Tumors of the esophagus are located in the thoracic cavity;
- Pre-treatment stage as clinical II-III (AJCC/UICC 8th Edition)
- Age is between 18 years and 75 years;
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and expected survival time ≥12 months;
- 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 %;
- Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in pulmonary function tests ;
- Adequate bone marrow function (White Blood Cells \>4x10\^9 /L; Neutrophil \>2.0×10\^9 /L; Hemoglobin \> 90 g/L; platelets\>100x10\^9 /L);
- Adequate liver function (Total bilirubin \<1.5x Upper Level of Normal (ULN); Aspartate transaminase(AST) and Alanine transaminase (ALT) \<1.5x ULN);
- Adequate renal function (Glomerular filtration rate (CCr) \>60 ml/min; serum creatinine (SCr) ≤120 µmol/L);
- The patient has provided written informed consent and is able to understand and comply with the study;
Exclusion Criteria17
- Patients with histological non-squamous cell carcinoma;
- Patients with advanced non-operable or metastatic esophageal cancer;
- 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;
- 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;
- Patients who have received or are receiving other chemotherapy, radiotherapy or targeted therapy;
- Patients with autoimmune diseases history;
- Recently or currently taking Glucocorticoids or Immunosuppressants;
- Patients who underwent immunotherapy in the past;
- Allergy to any antibody drugs or allergy to Paclitaxel and Carboplatin.
- Past or currently suffering from chronic or recurrent autoimmune diseases;
- 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;
- Patients with organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation);
- 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;
- 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;
- Pregnant or lactating women and fertile women who will not be using contraception during the trial;
- 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;
- Expected lack of compliance with the protocol.
Interventions
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 (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);
After neoadjuvant therapy, patients in groups receive Ivor-Lewis or Mckeown Esophagectomy (Mckeown Esophagectomy recommended)
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT04973306