Chemoradiation Plus tisLelizumAb for Conversion Therapy of Locally Nonresectable ESCC
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Treatment safety
研究概览
简要总结
This is a single institution and single-arm phase I/II study to assess the feasibility and efficacy of tislelizumab plus chemoradiation for conversion therapy of patients with locally nonresectable ESCC.
详细描述
The success of PD-1 antibody immunotherapy has brought about tremendous changes in clinical practice for treating patients with ESCC. Many patients with ESCC were not resectable at first presentation because of locally advanced disease in the primary site and/or in lymph nodes. The primary intention of our study was to evaluate the feasibility and efficacy of combining tislelizumab and chemoradiation for conversion therapy for these patients. The enrolled patients in this study should be with pathologically proved ESCC staged IIIb-IVa according to the 8th edition of UICC/AJCC TNM stage classification. This is a single institution and single-arm phase I/II study, the estimated enrollment was 30 participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed ESCC；
- •Clinical stage T4 N-/+，or T1-3 N+（IIIb-IVa） (AJCC 8 TNM classiftion);
- •Locally advanced ESCC that are not resectable for primary site and/or lymph nodes evaluated before treatment;
- •At least one measurable lesion in accordance with RECIST 1.1;
- •Have a performance status of 0 or 1 on the ECOG Performance Scale;
- •Expected survival time is greater than 6 months;
- •The important organs' functions meet the following requirements: the absolute neutrophil count(ANC) ≥1.5×10^9/L; the platelet count ≥100×10^9/L; hemoglobin ≥90g/L; bilirubin is less than or equal to 1.5 times ULN, ALT and AST less than or equal 2.5 times UILN; creatinine clearance rate (CCr) ≥50mL/min; the thyroid function is normal;
- •Female subjects of childbearing potential have a negative pregnancy test and must agree to take effective contraceptive measures during the study period and within 3 months after the last dose;
- •Be willing and able to provide written informed consent/assent for the trial.
排除标准
- •The patient has received radiotherapy, chemotherapy, hormone therapy, surgery, or molecular-targeted therapy;
- •Confirmed patients with distant metastasis by CT imaging;
- •The subject has previous or co-existing other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
- •The subject had previously received other anti-PD-1 antibody therapy or other immunotherapy targeting PD-1 / PD-L1;
- •Patients with active autoimmune disease or documented autoimmune disease or symptoms requiring systemic hormone therapy or anti-autoimmune drug therapy;
- •Patients with immunodeficiency or who were still receiving systemic steroid hormone therapy (prednisone > 10 mg/ day or other equivalent drugs) or other forms of immunosuppressive therapy 7 days prior to the first dose of neoadjuvant therapy in this study;
- •Clinical ascites or pleural effusion requiring therapeutic puncture or drainage;
- •The subject with uncontrol cardiac clinical symptoms or diseases, such as (1) any class 2 or more heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant ventricular or ventricular arrhythmias requiring treatment or intervention;
- •Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg> 2G /L), bleeding tendency, or receiving thrombolytic or anticoagulant treatment;
- •The subject is present (within 3 months) with esophageal varices, active gastric and duodenal ulcers, ulcerative colitis, portal hypertension, and other gastrointestinal diseases, or with active bleeding from unresected tumors, or other conditions that may cause gastrointestinal bleeding or perforation as determined by the investigator;
- •Past or present severe bleeding (bleeding >30 ml within 3 months), hemoptysis (fresh blood >5 ml within 4 weeks) or thromboembolism events (including stroke events and/or TRANSIENT ischemic attack) within 12 months;
- •Patients with active infection who still required systemic treatment 7 days before the first dose of neoadjuvant therapy in this study;
- •Patients with past or present objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radioactive pneumonia, drug-related pneumonia, severely impaired lung function, etc;
- •Senior or uncontrolled virus injection: HIV, TP, hepatitis virus;
- •Patients who had participated in clinical trials of other drugs within 4 weeks;
- •The live vaccine was administered less than 4 weeks prior to study administration or possibly during the study period;
- •Have a history of mental illness or psychiatric substance abuse;
- •The subject cannot or does not agree to bear the cost of the self-paid portion of the examination and treatment, except for the clinical study drug, combined chemoradiotherapy, and SAE associated with the clinical study drug;
- •Other patients whom the medical practitioner considers inappropriate for inclusion.
研究组 & 干预措施
Tislelizumab plus chemoradiation group
In the single experimental arm, patients with nonresectable stage IIIb-IVa disease were subjected to receive neoadjuvant tislelizumab (200mg) plus chemoradiation (TP regimen plus 30Gy/12F irradiation) for conversion therapy. If conversion therapy succeeds, patients would proceed to surgery and adjuvant therapy. Otherwise, if patients were still not resectable after the conversion therapy, an additional radiation dose of 15Gy/6F would be scheduled for the ESCC lesions to achieve a definite radiotherapy dose, then, patients proceeded to consolidation therapy.
干预措施: Tislelizumab (Drug)
Tislelizumab plus chemoradiation group
In the single experimental arm, patients with nonresectable stage IIIb-IVa disease were subjected to receive neoadjuvant tislelizumab (200mg) plus chemoradiation (TP regimen plus 30Gy/12F irradiation) for conversion therapy. If conversion therapy succeeds, patients would proceed to surgery and adjuvant therapy. Otherwise, if patients were still not resectable after the conversion therapy, an additional radiation dose of 15Gy/6F would be scheduled for the ESCC lesions to achieve a definite radiotherapy dose, then, patients proceeded to consolidation therapy.
干预措施: Paclitaxel (Drug)
Tislelizumab plus chemoradiation group
In the single experimental arm, patients with nonresectable stage IIIb-IVa disease were subjected to receive neoadjuvant tislelizumab (200mg) plus chemoradiation (TP regimen plus 30Gy/12F irradiation) for conversion therapy. If conversion therapy succeeds, patients would proceed to surgery and adjuvant therapy. Otherwise, if patients were still not resectable after the conversion therapy, an additional radiation dose of 15Gy/6F would be scheduled for the ESCC lesions to achieve a definite radiotherapy dose, then, patients proceeded to consolidation therapy.
干预措施: Carboplatin (Drug)
Tislelizumab plus chemoradiation group
In the single experimental arm, patients with nonresectable stage IIIb-IVa disease were subjected to receive neoadjuvant tislelizumab (200mg) plus chemoradiation (TP regimen plus 30Gy/12F irradiation) for conversion therapy. If conversion therapy succeeds, patients would proceed to surgery and adjuvant therapy. Otherwise, if patients were still not resectable after the conversion therapy, an additional radiation dose of 15Gy/6F would be scheduled for the ESCC lesions to achieve a definite radiotherapy dose, then, patients proceeded to consolidation therapy.
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Treatment safety
时间窗: up to 2 years
The incidence and severity of treatment related adverse event according to CTCAE 5.0
次要结局
- Objective response rate (ORR)(up to 2 years)
- Conversion esophagectomy rate (CER)(up to 2 years)
- Major pathological response (MPR)(up to 2 years)
- Progression free survival (PFS)(up to 2 years)
- Overall survival (OS)(up to 2 years)
研究者
Hongliang Yu
Dr.
Jiangsu Cancer Institute & Hospital