A Prospective Single-arm Multi-center Phase II Study: Assessment of the Safety and Abscopal Effects of SBRT in Combination With rhGM-CSF for Stage IV NSCLC Patients Who Failed in Second-line Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- abscopal effect rate
研究概览
简要总结
The purpose of this study is to determine whether stereotactic body radiotherapy (SBRT) combined with recombined human granulocyte-macrophage colony stimulating factor(rhGM-CSF) is safe, effective in the treatment of stage IV NSCLC patients who failed in second-line chemotherapy.
详细描述
Metastasis lesion will be treated with a SBRT of 50Gy/5F from day 1 to day 5 in one cycle.Subcutaneous injection of human recombined granulocyte-macrophage colony stimulating factor (125ug/m² per day) will be executed from day 1 to day 14 in this cycle. Another metastasis lesion will be treated likewise concurrently with rhGM-CSF in a consecutive cycle. Efficacy evaluation,especially abscopal effect evaluation, will be conducted at the end of therapy and every month after that. Adverse events will be recorded according to NCI-CTC version 4.03.
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 proven non-small-cell lung cancer.
- •Stage IV according to UICC stage system(version 7,2009).
- •Progression after standard second-line chemotherapy.
- •At least Three evaluable lesions among which at least two must be suitable for SBRT.
- •ECOG performance status 0-
- •Expected lifespan ≥3 months.
- •Stable lab values:
- •Hematological: Absolute neutrophil count (ANC) ≥1.5×109/L, Platelets ≥100×109/L, Hemoglobin ≥9 g/dL Renal: Creatinine OR Measured or calculated creatinine clearance (CrCl) (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) ≤1.5× the upper limit of normal (ULN) OR ≥60 mL/min for patient with creatinine levels >1.5× institutional ULN Hepatic: Total bilirubin ≤1.5×ULN OR Direct bilirubin ≤ULN for patients with total bilirubin levels >1.5×ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN OR ≤5×ULN for patients with liver metastases ,globulin≥20 g/L, albumin≥30 g/L.
- •Female subjects must have a negative urine or serum pregnancy test within 72 hours prior to taking study drug if of childbearing potential.
- •Able to understand and give written informed consent and comply with study procedures.
- •Exclusion criteria:
- •Any unstable systemic disease, including active infection, uncontrolled high blood pressure, unstable angina, newly observed angina pectoris within the past 3 months, congestive heart failure (New York heart association (NYHA) class II or higher), myocardial infarction onset six months before included into the group, and severe arrhythmia, liver, kidney, or metabolic disease in need of drug therapy.
- •Any clinical evidence suggests moderately severe chronic obstructive pulmonary disease (COPD) - [With COPD history or related risk factors, FEV1 / FVC < 70%, FEV1 < 80% estimated value, with or without chronic cough, sputum, dyspnea symptoms), active interstitial lung disease - ILD (FEV1 / FVC < 70%, FEV1 < 80% estimated value, carbon monoxide diffusion capacity in lung - DLCO < 40%, and high resolution CT (HRCT) confirmed as the diffuse pulmonary interstitial lesions] and other active pulmonary disease.
- •Previously diagnosed with autoimmune diseases, including but not limited to systemic lupus erythematous, rheumatoid arthritis, systemic vasculitis, scleroderma, dermatomyositis, autoimmune hemolytic anemia and autoimmune liver disease, autoimmune thyroiditis.
- •Human immunodeficiency virus (HIV) infection.
- •Women in pregnancy or lactation .
- •Medicine abusers(including alcohol, drugs or other addictive drugs abusers).
- •Patients with mental illness, considered as "can't fully understand the issues of this research".
- •Cancer history within 5 years apart from NSCLC before enrollment.
- •Histologically confirmed small cell carcinoma or other non NSCLC compositions in the cancer tissue.
- •Cancer treatment within 4 weeks, including but not limited to palliative surgery ,radiotherapy, chemotherapy and target therapy.
- •Tumor related immunotherapy within 1 year, including but not limited to immune cell therapy, tumor vaccine therapy, immune check-point monoclonal antibody related treatment, and cytokines treatment except for GM-CSF.
- •Allergy of rhGM-CSF and its accessories.
- •Contraindications to GM-CSF treatment.
- •Patients with unilateral lung.
排除标准
- 未提供
研究组 & 干预措施
SBRT+GM-CSF
Metastasis lesion will be treated with a SBRT of 50Gy/5F from day 1 to day 5 in a cycle of 21 days.Subcutaneous injection of human recombined granulocyte-macrophage colony stimulating factor (125ug/m² per day) will be executed from day 1 to day 14 in this cycle. Another metastasis lesion will be treated likewise concurrently with rhGM-CSF in a consecutive cycle.
干预措施: Stereotactic body radiotherapy (Radiation)
SBRT+GM-CSF
Metastasis lesion will be treated with a SBRT of 50Gy/5F from day 1 to day 5 in a cycle of 21 days.Subcutaneous injection of human recombined granulocyte-macrophage colony stimulating factor (125ug/m² per day) will be executed from day 1 to day 14 in this cycle. Another metastasis lesion will be treated likewise concurrently with rhGM-CSF in a consecutive cycle.
干预措施: rhGM-CSF (Drug)
结局指标
主要结局
abscopal effect rate
时间窗: at the time point of 4 weeks after completion of rhGM-CSF
次要结局
- overall survival(2 years)
- Incidence of Adverse events(2 years)
- progression free survival(2 years)
- objective response rate(2 years)
- abscopal effect rate(at the time point of 2 months after completion of rhGM-CSF)
- Incidence of treatment-related adverse events(2 years)
- Incidence of immune-related adverse events(2 years)
研究者
Conghua Xie,MD,PhD
Professor,MD,PhD,Director of Department of Radiation and Medical Oncology,Zhongnan Hospital
Wuhan University