A Phase II Trial of Hypofractionated Radiotherapy for Limited Metastatic NSCLC Harboring Sensitizing EGFR Mutations After First Line TKI Therapy
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 76
- 主要终点
- Progression free survival
研究概览
简要总结
To evaluate the efficacy and toxicity of patients treated with hypofractionated radiotherapy for limited metastatic NSCLC harboring sensitizing EGFR mutations after first line TKI therapy. An exploratory biomarker analysis in blood and tumor samples is also planned.
详细描述
Rational:
After inductive TKI therapy in NSCLC with sensitizing EGFR mutations, the residual lesion might be the source of subsequent disease progression, defined as acquired resistance to TKI. Two reasons can be used to explain the formation of the residual lesion：1）there is a subgroup of cancer cells that are not sensitive to TKI therapy because of tumor heterogeneity, like de novo T790M mutation; 2)some cancer cells can keep static state during the beginning treatment, and then develops acquired resistance to TKI therapy under the long-term drug pressure and continue to re-proliferation. From this point of view, elimination of residual lesion provides the chance to reduce or slow the possibility of developing resistance to TKI.
Objective
To evaluate the efficacy and toxicity of patients treated with hypofractionated radiotherapy for limited metastatic NSCLC harboring sensitizing EGFR mutations after first line TKI therapy. An exploratory biomarker analysis in blood and tumor samples is also planned.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed metastatic lung adenocarcinoma harboring sensitizing EGFR mutations (L858R, exon 19 deletion), and became oligometastatic disease after 3 months TKI, evaluated by PET/CT scan, brain MRI, and abdomen ultrasound (≤6 discrete lesions of disease, exclusive of the brain metastases, ≤3 lesions in the liver, ≤3 lesions in the lung);
- •All sites of disease must be amenable to definitive RT;
- •An intrathoracic lymph nodal station is considered 1 discrete lesion, according to IASLC lymph nodal station map;
- •Age 18 years or older;
- •ECOG Performance Status 0-2;
- •Adequate bone marrow, liver and renal function, as specified below: Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L; Hemoglobin ≥ 8 g/dL; Platelets ≥ 100 x 109/L; Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) ; AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present; Serum creatinine ≤ 1.5 x upper limit of normal or creatinine clearance ≥ 60ml/min for patients with creatinine levels above institutional normal;
- •For women of child-bearing potential, negative pregnancy test within 14 days prior to starting treatment;
- •Men and women of childbearing age must be willing to use effective contraception while on treatment and for at least 3 months thereafter;
- •Patients and their family signed the informed consents;
排除标准
- •Received chemotherapy before TKI therapy;
- •Brain parenchyma or leptomeningeal disease;
- •Any site of disease that is not amenable to definitive RT;
- •Concurrent malignancies other than non-melanoma skin cancer that require active ongoing treatment;
- •Any medical co-morbidities that would preclude radiation therapy.
研究组 & 干预措施
EGFR-TKI+hypofractionated radiotherapy
After 3 mos TKI, patients with limited metastatic take EGFR-TKI concurrent with hypofractionated radiotherapy till tumor progression.
干预措施: Thoracic Hypofractionated Radiotherapy (Radiation)
EGFR-TKI
Patients take EGFR-TKI alone till tumor progression
干预措施: EGFR-TKI (Drug)
EGFR-TKI+hypofractionated radiotherapy
After 3 mos TKI, patients with limited metastatic take EGFR-TKI concurrent with hypofractionated radiotherapy till tumor progression.
干预措施: EGFR-TKI (Drug)
结局指标
主要结局
Progression free survival
时间窗: 3 years
次要结局
- Frequency of T790M mutation after 1 year detected by ctDNA(1 year)
- To assess the short-term quality of life (QOL)(4 months)
- Frequency of T790M mutation before treatment detected by ctDNA(1 months)
- Abundance of T790M mutation before treatment detected by ctDNA(1 months)
- Frequency of T790M mutation after radiotherapy detected by ctDNA(3 months)
- Abundance of T790M mutation after radiotherapy detected by ctDNA(3 months)
- Abundance of T790M mutation after 1 year detected by ctDNA(1 year)
- Rate of CTCAE grade 2 or higher radiation pneumonitis(1 years)