Phase III Study to Evaluate the Optimal Timing of Postoperative Radiotherapy for High Risk of Locoregional Recurrence Patients With Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 132
- 试验地点
- 1
- 主要终点
- Disease-free survival (DFS)
研究概览
简要总结
Rationale: Completely resected non-small cell lung cancer (NSCLC) patients with histologically confirmed N2 disease are a heterogeneous population. After complete resection and postoperative chemotherapy (POCT), 20%-40% of cases have a risk of locoregional recurrence (LRR). Postoperative radiation therapy (PORT) should be an integral component of the multidisciplinary treatment for patients with stage IIIA(N2) disease. Postoperative Radiotherapy (PORT)-first strategy may have an advantage of the early administration of locoregional therapy to the mediastinum, in which the tumor burden is presumed to be higher than that of systematic micrometastases. It is not yet known for subsets with specific prognostic factors that confer higher LRR risks, what is the optimal timing of PORT and how to integrate with POCT (in a sequential fashion or concurrent fashion) when PORT is considered for patients with completely resected stage IIIA(N2) NSCLC.
Purpose: This randomized phase III trial is studying the optimal timing of PORT to evaluate whether the PORT-first strategy (PORT administered first with concurrent or subsequent POCT) may be more effective than the PORT-last strategy (PORT administered sequentially following POCT) in treating high risk of LRR patients with completely resected pathologic stage IIIA(N2) NSCLC.
详细描述
OBJECTIVES:
- Primary
- Investigate the optimal timing of PORT for completely resected pathologic stage IIIa(N2) NSCLC by comparing the disease-free survival of patients with high risk of LRR treated with PORT-first vs PORT-last strategy.
- Secondary
- Determine the overall survival of patients treated with these regimens.
- Compare the locoregional recurrence-free survival in patients treated with these regimens.
- Compare the distant metastasis-free survival in patients treated with these regimens.
- Determine patterns of failure in patients treated with these regimens.
- Determine the toxicity, in particular cardiac and pulmonary toxicity, of these regimens in these patients.
- Determine the prediction models for locoregional recurrence and brain metastasis based on the clinical, pathological, radiological, genetic, tumor microenvironmental and immunological data.
OUTLINE: This is a multicenter, randomized study. The clinical risk prediction model for LRR has been established based on our large institutional database. On multivariate analysis, heavy cigarette smoking history, cN2 status, and number of involved lymph nodes>4 were independently significant factors predicting high risk of LRR. The Prognostic Index (PI) equation was built including the three categorical variables and coefficients based on their level of significance: PI＝(0.9×smoking history)＋(0.5×clinical N status)＋(0.8×number of involved lymph nodes). Patients with the PI score≥3.5 were considered as high risk of LRR.
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
- •Male or female, aged 18 years to 75 years;
- •Complete resection through a surgical procedure of lobectomy, sleeve lobectomy or bilobectomy with microscopically tumor-free resection margins and margin-negative resection of all gross disease; Has undergone systematic nodal assessment (lymph node dissection or sampling with a minimum of three N2 stations sampled or completely dissected, one of which must be the subcarinal station);
- •Histologically proven lung adenocarcinoma or squamous cell lung carcinoma of stage pT1-3N2M0 (according to the TNM classification in the Union for International Cancer Control (UICC) 7th ed.);
- •Determined as the postoperative high risk of locoregional recurrence;
- •No documented metastases (M1) and/or invasion (T4) by the pretreatment examination or at the time of surgery;
- •No prior neoadjuvant therapy (chemotherapy and/or RT);
- •No prior adjuvant therapy (chemotherapy and/or RT);
- •No severe perioperative complications and expected postoperative lifespan ≥4 months;
- •ECOG Performance Status 0-1;
- •Voluntarily participated in this study and signed the informed consent form by himself or his agent. Had good compliance with the study procedures, and can cooperate with the relevant examination, treatment and follow-up;
排除标准
- •Histologically confirmed large cell carcinoma, adenosquamous carcinoma, sarcomatoid carcinomas, neuroendocrine tumors (small cell carcinoma, large cell neuroendocrine carcinoma, carcinoid tumors, etc.), salivary-gland type tumors, adenomas, papillomas, or other and unclassified carcinomas;
- •Patients undergoing pneumonectomy;
- •Diagnosed with other prior or concurrent malignancies (neoplasm) except for basal cell carcinoma of the skin or carcinoma in situ of the cervix within the last 5 years;
- •Patients with severe postoperative complications; and time to beginning of the adjuvant therapy has been more than 2 months from the date of surgery;
- •Patients with any severe or uncontrolled systematic disease including severe cardiovascular, liver, kidney, hematopoietic, metabolic disease, or uncontrolled active infection that would preclude study participation;
- •Patients with positive mental disorder that would preclude study participation;
- •Contradictory to chest radiotherapy;
- •Pregnant or nursing women;
- •Concurrent other anti-cancer treatment;
- •Prior preoperative Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) treatment or other targeted therapy;
研究组 & 干预措施
Arm I (PORT-first strategy)
Concurrent chemoradiotherapy + sequential chemotherapy or PORT + sequential chemotherapy: Participants in the Arm I will receive PORT at the first day of therapy. For lung adenocarcinoma, the first day of radiotherapy will be administered concurrently with chemotherapy (two cycles of chemotherapy given during radiotherapy); then continue to give two cycles of sequential chemotherapy. For squamous cell lung carcinoma, PORT will be administered first followed by subsequent four cycles of sequential chemotherapy.
干预措施: PORT-first (Radiation)
Arm I (PORT-first strategy)
Concurrent chemoradiotherapy + sequential chemotherapy or PORT + sequential chemotherapy: Participants in the Arm I will receive PORT at the first day of therapy. For lung adenocarcinoma, the first day of radiotherapy will be administered concurrently with chemotherapy (two cycles of chemotherapy given during radiotherapy); then continue to give two cycles of sequential chemotherapy. For squamous cell lung carcinoma, PORT will be administered first followed by subsequent four cycles of sequential chemotherapy.
干预措施: Platinum-based two drug chemotherapy (cisplatin/carboplatin + vinorelbine or cisplatin/carboplatin + pemetrexed regimen) (Drug)
Arm II (PORT-last strategy)
Four cycles of chemotherapy + sequential PORT: Participants in the Arm II will receive four cycles of adjuvant chemotherapy and after that, sequential PORT (50.4 Gy, 1.8 Gy once daily over 5.5 weeks) will be administered.
干预措施: PORT-last (Radiation)
Arm II (PORT-last strategy)
Four cycles of chemotherapy + sequential PORT: Participants in the Arm II will receive four cycles of adjuvant chemotherapy and after that, sequential PORT (50.4 Gy, 1.8 Gy once daily over 5.5 weeks) will be administered.
干预措施: Platinum-based two drug chemotherapy (cisplatin/carboplatin + vinorelbine or cisplatin/carboplatin + pemetrexed regimen) (Drug)
结局指标
主要结局
Disease-free survival (DFS)
时间窗: 4 years
次要结局
- Locoregional recurrence-free survival (LRFS)(4 years)
- Distant metastasis-free survival (DMFS)(4 years)
- Overall survival (OS)(4 years)
- Treatment-related adverse event(1 year)
研究者
Xiaolong Fu
Director, Department of Radiation Oncology
Shanghai Chest Hospital