Randomized Phase III Trial Investigating the Survival Benefit of Adding Thoracic Radiotherapy to Durvalumab (MEDI4736) Immunotherapy Plus Chemotherapy in Extensive Stage Small-cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 239
- 试验地点
- 20
- 主要终点
- Change in 1-year overall survival
研究概览
简要总结
Studies have shown that combining chemotherapy and immune checkpoint inhibitors (ICI) prolongs survival compared with chemotherapy alone in extensive stage small-cell lung cancer (ES SCLC), but the survival benefit is modest. The main aim of this trial is to investigate whether there is a synergistic/additive effect of concurrent thoracic radiotherapy in ES SCLC patients receiving carboplatin/etoposide/durvalumab.
详细描述
Studies show that adding ICI therapy to standard chemotherapy prolongs survival in ES SCLC. The survival benefit, however, is modest, and there is a need for more effective therapy. It has been hypothesized that there is a synergistic effect of combining ICI with radiotherapy. In this randomized phase III study, the main aim is to investigate whether concurrent thoracic radiotherapy of 30 Gy/10 fractions improves survival in ES SCLC patients receiving carboplatin/etoposide/durvalumab.
It is currently not possible to classify the patients who benefit from ICIs in SCLC. In this study, biological material (tissue, blood, feces) which will be analyzed for potential predictive and prognostic biomarkers.
Prophylactic cranial irradiation in ES SCLC is debated, mainly due to the potentially detrimental effect on cognition. Thus, frequency and timing of brain metastases and cognitive function will be assessed before, during and after study treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years at time of study entry
- •ECOG performance status of 0 or 1
- •Body weight >30 kg
- •Adequate bone marrow, liver and kidney function
- •Life expectancy of at least 3 months
- •At least one measurable (RECIST 1.1), thoracic lesion that can be irradiated with 30 Gy/10 fractions
- •Histologically or cytologically confirmed SCLC
- •Stage III-IV disease (TNM v8)
- •FEV1 >1 L or >30 % of predicted value and DLCO >30 % of predicted value
- •Patients with brain metastases are eligible provided they are asymptomatic or treated and stable on steroids and/or anticonvulsants prior to the start of treatment
排除标准
- •Previous chemo-, immuno- or radiotherapy for SCLC
- •Major surgical procedure last 28 days
- •History of allogenic organ transplantation, autoimmune disease, immunodeficiency, hepatitis or HIV
- •Uncontrolled intercurrent illness
- •Other active malignancy
- •Leptomeningeal carcinomatosis
- •Immunosuppressive medication
- •Pregnant or breastfeeding women
研究组 & 干预措施
Chemo-immunotherapy plus thoracic radiotherapy
Four courses of carboplatin/etoposide/durvalumab every 3 weeks followed by durvalumab every 4 weeks until intolerable toxicity, progressive disease leading to a need for other treatment, or until the patient no longer wishes to continue treatment.
Thoracic radiotherapy of 30 Gy/10 fractions between 2nd and 3rd carboplatin/etoposide/durvalumab course.
干预措施: Thoracic radiotherapy (Procedure)
Chemo-immunotherapy plus thoracic radiotherapy
Four courses of carboplatin/etoposide/durvalumab every 3 weeks followed by durvalumab every 4 weeks until intolerable toxicity, progressive disease leading to a need for other treatment, or until the patient no longer wishes to continue treatment.
Thoracic radiotherapy of 30 Gy/10 fractions between 2nd and 3rd carboplatin/etoposide/durvalumab course.
干预措施: Chemo-immunotherapy (Drug)
Chemo-immunotherapy
Four courses of carboplatin/etoposide/durvalumab every 3 weeks followed by durvalumab every 4 weeks until intolerable toxicity, progressive disease leading to a need for other treatment, or until the patient no longer wishes to continue treatment.
干预措施: Chemo-immunotherapy (Drug)
结局指标
主要结局
Change in 1-year overall survival
时间窗: 14 months after last patient entry
The Cox proportional hazards method will be used to compare survival between the treatment groups.
次要结局
- Change in overall response rates(Through study completion, an average of 1 year after last patient entry)
- Local control rates in the thorax(Through study completion, an average of 1 year after last patient entry)
- Change in progression free survival (PFS)(Through study completion, an average of 1 year after last patient entry)
- Change in 2-, 3-, 4- and 5-year survival rate(2, 3, 4 and 5 years after last patient entry)
- Frequency and severity of adverse events(Through study completion, an average of 1 year after last patient entry)
- Change in response rates in non-irradiated lesions(Through study completion, an average of 1 year after last patient entry)
- Health-related quality of life (HRQoL)(Through study completion, an average of 1 year after last patient entry)