Durvalumab Combined With Chemoradiotherapy for Limited Stage Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Assessment of the incidence of treatment-related adverse events Incidence of Treatment-Emergent Adverse Events.
研究概览
简要总结
This trial aims to assess efficacy and safety of durvalumab combined with chemoradiotherapy for limited stage small cell lung cancer.
详细描述
Small cell lung cancer is a highly malignant tumor that accounts for about 15% of all lung cancer types. The 5-year survival rate is less than 5%, and the overall survival of patients who do not receive any antitumor therapy is only 2-4 months. In the past 40 years, 4 to 6 cycles of platinum-based chemotherapy, that is, etoposide combined with cisplatin or carboplatin, has become the standard therapy for small cell lung cancer patients and has been recommended by major global tumor treatment guidelines. While initial response rates are as high as 70%, 80% of limited-stage patients and nearly all patients with extensive stages are found to experience relapse or disease progression. Current guidelines recommend that patients with limited stage small cell lung cancer adopt the EP regimen combined with thoracic radiotherapy as the preferred treatment for patients with limited stage small cell lung cancer. PD-L1 is part of a complex system of receptors and ligands involved in controlling T cell activation. PD-L1 acts at multiple sites in the body, releasing inhibitory signals to T cells via the PD-1 and CD80 receptors to help regulate the immune response. Durvalumab is an immunoglobulin G (IgG) 1-κsubtype monoclonal antibody (mAb) that blocks the interaction of PD-L1 with PD-1 in T cells and CD80 (B7.1) in immune cells (ics). This trial aims to assess efficacy and safety of durvalumab combined with chemoradiotherapy for limited stage small cell lung cancer.
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
- •Voluntary participation and written signed informed consent;
- •Age 18-75 years old, gender is not limited;
- •Histologically or cytologically confirmed limited-stage small cell lung cancer (2009 AJCC/UICC/IASLC lung cancer TNM staging criteria, limited-stage SCLC is any T stage, any N stage, and M0), and patients with suspected brain or bone metastasis at the time of screening should undergo brain MRI or ECT before study enrollment;
- •There are immunohistochemical results;
- •Chemotherapy must include either cisplatin or carboplatin, in combination with etoposide;
- •Physical status score ECOG 0-1;
- •Weight > 40 kg;
- •Expected survival ≥ 6 months;
- •According to RECIST 1.1 guidelines, at least one lesion (not previously receiving radiotherapy) with a maximum diameter ≥ 10 mm as accurately measured by computed tomography (CT) or magnetic resonance imaging (MRI) at baseline (except lymph nodes, whose short axis must be ≥ 15 mm); And the lesion is suitable for repeated accurate measurement.;
- •No previous immunotherapy;
- •no serious abnormalities of haematopoietic, cardiac, pulmonary, hepatic; and renal functions and immunodeficiency (Haematology: white blood cells ≥3.5×109/L; neutrophils ≥1.5×109/L; haemoglobin ≥90g/L; platelets
- •≥100×109/L. Liver and kidney function: total bilirubin ≤1.5 times the upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) ≤2.5 times the upper limit of normal; creatinine ≤1.5 times the upper limit of normal; albumin ≥30 g/L. Coagulation: International Normalised Ratio (INR) or Prothrombin Time (PT) or Activated Partial Thromboplastin Time (APTT)
- •≤ 1.5 times ULN; if the subject is receiving anticoagulation therapy, PT or INR is acceptable as long as the PT or INR is within the range of the anticoagulant drug formulation. Echocardiographic assessment: left ventricular ejection fraction (LVEF) ≥ low limit of normal (50%). Pulmonary function FEV1 ≥70% of % of predicted value and DLCO ≥60% of % of predicted value).
- •The female patient has evidence of postmenopausal status, or the urine or serum pregnancy test results of the premenopausal woman are negative. Women who stop menstruating for 12 months without other medical reasons are considered menopausal.
排除标准
- •Distant organ metastases (excluding supraclavicular lymph nodes) as determined by CT evaluation during screening and prior imaging;
- •have received prior radiotherapy to the chest;
- •have medical contraindications to etoposide - platinum (carboplatin or cisplatin) based chemotherapy;
- •having any active autoimmune disease or a history of autoimmune disease (e.g. interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary gland inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (which can be included if hormone replacement therapy is effective), etc.), and a history of immunosuppressive drug use within 28 days, with the exception of the use of hormones for the purpose of dealing with toxicity from radiotherapy;
- •Previously received or are receiving other PD-1 antibody therapy or other immunotherapy targeting PD-1/PD-L1, or are currently participating in other interventional clinical studies for treatment;
- •Have received other anti-tumour therapy (including herbal therapy with anti-tumour effect) within 4 weeks prior to the first dose of the study; have received long-term systemic immunotherapy or hormone therapy (except physiological replacement therapy, e.g., oral thyroxine for hypothyroidism) within 4 weeks prior to the first dose of the study; and have been treated with other experimental drugs or interventional clinical studies within 4 weeks prior to the first dose of the study;
- •Patients with uncontrolled clinical cardiac symptoms or disease such as
- •(1) NYHA class II or higher heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, and (4) clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention;
- •with congenital or acquired immune function defects (e.g., HIV-infected patients), active hepatitis B (HBV-DNA ≥104 copies/ml) or hepatitis C (hepatitis C antibody-positive with HCV-RNA above the lower limit of detection of the analytical method), or active tuberculosis;
- •Have an active infection or unexplained fever >38.5°C within 2 weeks prior to screening (at the investigator's discretion, subjects may be enrolled for fever arising from tumours);
- •In the judgement of the investigator, the subject has other factors that may cause him/her to be forced to terminate the study in the middle of the study, e.g., suffering from other serious illnesses (including psychiatric illnesses) that require comorbid treatment, family or social factors that may affect the safety of the subject or the collection of trial data.
研究组 & 干预措施
D with CRT
The patients with limited stage small cell lung cancer receive durvalumab combined with chemoradiotherapy.
干预措施: Durvalumab (Drug)
D with CRT
The patients with limited stage small cell lung cancer receive durvalumab combined with chemoradiotherapy.
干预措施: Chemotherapy drug of EP regimen (Drug)
D with CRT
The patients with limited stage small cell lung cancer receive durvalumab combined with chemoradiotherapy.
干预措施: radiotherapy (Radiation)
结局指标
主要结局
Assessment of the incidence of treatment-related adverse events Incidence of Treatment-Emergent Adverse Events.
时间窗: Treatment with durvalumab for at least 1 year, or until progression, intolerance, or spontaneous withdrawal of patients.
Adverse events are observed during the course of the study and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE V5.0).
Assessment of objective remission rate (ORR) in limited stage small cell lung cancer treated with durvalumab combined with chemoradiotherapy
时间窗: Treatment with durvalumab for at least 1 year, or until progression, intolerance, or spontaneous withdrawal of patients.
Objective tumor remission is assessed by the investigator using the Solid Tumor Remission Assessment Criteria (RECIST 1.1 criteria). Objective remission rate (ORR): defined as the proportion of subjects whose tumor volume shrinks to a pre-specified value and can be maintained for the minimum time frame required, incorporating cases in complete remission (CR) and partial remission (PR).
次要结局
- Assessment of overall survival (OS) in limited stage small cell lung cancer.(Treatment with durvalumab for at least 1 year, or until progression, intolerance, or spontaneous withdrawal of patients.)
- Assessment of progression-free survival (PFS) in limited stage small cell lung cancer.(Treatment with durvalumab for at least 1 year, or until progression, intolerance, or spontaneous withdrawal of patients.)
- Assessment of disease control rate (DCR) in limited stage small cell lung cancer.(Treatment with durvalumab for at least 1 year, or until progression, intolerance, or spontaneous withdrawal of patients.)