Spatially Fractionated Radiotherapy Combined With Chemo-immunotherapy for Locally Advanced Non-Small Cell Lung Cancer With Suboptimal Response to Initial Neoadjuvant Therapy: A Single-Arm, Open-Label, Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Objective response rate
研究概览
简要总结
Lattice radiation therapy (LRT) is a spatially fractionated thoracic radiotherapy technique that creates alternating high- and low-dose regions within primary lung tumors and metastatic lymph nodes to strengthen local tumor suppression and reduce radiation injury to normal thoracic organs. This study aims to evaluate the efficacy and safety of combining LRT with consolidation chemoimmunotherapy in unresectable stage III LA-NSCLC patients who show suboptimal tumor response to prior neoadjuvant chemoimmunotherapy, through a single-arm Phase II clinical trial. Patients will receive thoracic LRT delivered by a medical linear accelerator. High-dose spherical sub-targets will be contoured within the gross tumor volume of primary lung lesions and regional nodal metastases under standardized dose constraints to spare the lung, heart and esophagus. All enrolled subjects will receive sequential consolidation chemoimmunotherapy administered within one week after finishing LRT. Tumor response, treatment-related adverse events, local tumor control and long-term survival outcomes will be prospectively tracked throughout treatment and long-term follow-up.
详细描述
This open-label, single-arm Phase II clinical trial investigates the combination of lattice radiation therapy (LRT) and subsequent consolidation chemoimmunotherapy for patients with unresectable stage III locally advanced non-small cell lung cancer who only achieved limited tumor regression after standard neoadjuvant chemoimmunotherapy induction. LRT, a spatially fractionated radiotherapy technique, generates interleaved high- and low-dose zones inside tumor tissue to enhance local anti-tumor activity while minimizing radiation toxicity to surrounding healthy chest organs. Eligible participants will complete standardized thoracic LRT targeting primary lesions and involved lymph nodes following institutional contouring rules and dose restrictions. Consolidation chemoimmunotherapy will be initiated shortly after the end of radiotherapy. The study will continuously monitor all treatment-related and immune-related adverse events, evaluate therapeutic efficacy via regular imaging scans, and collect long-term survival data. Trial results will provide clinical evidence about the clinical value and safety profile of LRT plus consolidation chemoimmunotherapy for this high-risk LA-NSCLC subgroup with insufficient response to prior neoadjuvant systemic therapy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed unresectable stage III locally advanced non-small cell lung cancer (LA-NSCLC).
- •Received at least 2 cycles of standard neoadjuvant chemoimmunotherapy, with suboptimal tumor response verified by post-induction radiological evaluation.
- •Age ≥ 18 years old.
- •ECOG performance status of 0 or
- •Adequate hematologic, hepatic and renal function to complete radiotherapy and consolidation systemic therapy.
- •Voluntarily sign written informed consent and be capable of following study-related procedures.
排除标准
- •Prior thoracic radiotherapy history.
- •Active uncontrolled autoimmune disorders or persistent severe immune-related adverse events.
- •Untreated symptomatic brain metastases.
- •Severe irreversible cardiac, pulmonary, liver or renal dysfunction that cannot tolerate combined radiotherapy and immunotherapy.
- •Pregnant or breastfeeding women.
- •Concurrent or previous other malignant tumors within 5 years, except cured basal cell skin cancer and cervical carcinoma in situ.
- •Any absolute contraindication to lattice radiation therapy or immune checkpoint inhibitor.
研究组 & 干预措施
experimental group
Eligible patients with unresectable stage III LA-NSCLC who achieved suboptimal tumor response after prior neoadjuvant chemoimmunotherapy in this Phase II trial will receive thoracic lattice radiation therapy using a medical linear accelerator. Within the gross tumor volume (GTV) of primary lung lesions and metastatic regional lymph nodes, spherical high-dose LRT sub-targets will be delineated with fixed diameter and inter-target spacing standards. The LRT sub-targets must be contoured fully within the GTV, spare vital intrathoracic vessels, maintain a minimum safety margin from the outer GTV border, and account for a regulated volume percentage of the whole GTV. For thoracic tumor lesions, the D95 coverage of total GTV and individual LRT high-dose targets will follow defined per-fraction dose limits, while all efforts will be made to lower single-fraction radiation burden to lung, heart and esophagus organs at risk. After finishing the full course of lattice radiotherapy, standardized
干预措施: lattice radiation therapy (Radiation)
结局指标
主要结局
Objective response rate
时间窗: From enrollment up to 12 months after the last subject completes combination therapy
Objective response rate (ORR) assessed by RECIST version 1.1, calculated as the proportion of patients achieving complete response (CR) or partial response (PR) after combination therapy. Tumor lesions will be evaluated with contrast-enhanced CT scans of chest, abdomen and pelvis.
Pathological complete response
时间窗: From enrollment to 12 months after the last subject completes all study combination therapy
The proportion of patients achieving pathological complete response (pCR), defined as absence of viable residual tumor cells in post-treatment surgical resection specimens.
次要结局
- Major pathological response(From enrollment up to 12 months after the last subject completes combination therapy)
- R0 resection rate(From enrollment up to 12 months after the last subject completes combination therapy)
- Event-free survival(From enrollment up to 24 months after the last subject completes study treatment)
- Incidence of treatment-related adverse events(From enrollment through 30 days after completion of all study treatment)