Phase III Randomized Clinical Trial to Evaluate the Efficacy and Safety of Twice-Daily Hyperfractionated Dose-Escalated Thoracic Radiotherapy in Patients With Limited-Stage Small Cell Lung Cancer (ESCALADOR Study)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 300
- 试验地点
- 14
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This is a phase III clinical trial that aims to evaluate whether increasing the dose of radiotherapy given twice a day can improve treatment outcomes in patients with localized small cell lung cancer (SCLC). All patients will receive standard chemotherapy with cisplatin and etoposide and will be randomly assigned to one of three radiotherapy regimens.
The main objective is to determine whether this intensified radiotherapy improves progression-free survival and overall survival. The study will also compare two different dose escalation strategies and assess treatment side effects and patients' quality of life.
This research may help identify a more effective treatment approach for patients with limited-stage SCLC and could contribute to improving long-term survival in this aggressive type of cancer
详细描述
This is a phase III, prospective, randomized, multicenter trial designed to evaluate whether a dose escalation strategy using twice-daily hyperfractionated thoracic radiotherapy can improve outcomes in patients with limited-stage small cell lung cancer (LS-SCLC).
Patients will be randomly assigned to one of three treatment arms: (A) standard-dose radiotherapy (45 Gy in 30 fractions BID), (B) escalated-dose radiotherapy (60 Gy in 40 fractions BID), or (C) standard-dose with a simultaneous integrated boost (45-54 Gy BID). All patients will receive concurrent chemotherapy with cisplatin and etoposide.
The study aims to determine if intensified radiotherapy increases progression-free survival (PFS) and overall survival (OS). Secondary objectives include comparing toxicity profiles, quality of life (using EORTC QLQ-C30 and LC13/LC29), and exploratory analyses of circulating biomarkers.
LS-SCLC has high recurrence rates despite aggressive treatment. Although BID thoracic radiotherapy (TRT) of 45 Gy is considered standard, new evidence suggests that higher doses may further improve survival without increasing toxicity. Modern radiotherapy techniques and improved imaging (e.g., PET-CT) allow more accurate targeting and potential dose escalation.
The study plans to enroll 300 patients over 36 months across 10-15 Spanish centers, coordinated by the Instituto de Investigación Biomédica de Salamanca (IBSAL) and supported by SEOR-GOECP. An interim analysis will be conducted at year 1 and year 3, with a final analysis at 5 years. Data will be collected via REDCap and follow FAIR principles. The protocol has been approved by the Salamanca Research Ethics Committee.
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
- •Histologically confirmed diagnosis of small cell lung cancer (SCLC)
- •Limited-stage disease (Stage I-III; any T, any N, M0), eligible for definitive radiotherapy
- •Measurable disease according to RECIST 1.1
- •Age ≥18 years
- •ECOG performance status 0-2
- •No prior thoracic radiotherapy
- •Signed informed consent
- •Adequate hematologic function: WBC ≥3.0×10⁹/L, neutrophils ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥90 g/L
- •Adequate liver and renal function: total bilirubin ≤1.5×ULN, AST/ALT ≤1.5×ULN, creatinine normal or CrCl ≥60 mL/min
- •Pulmonary function: FEV1 >1 L or >30% predicted; DLCO >30% predicted
排除标准
- •Prior surgery or radiotherapy for any lung cancer (SCLC or NSCLC)
- •Presence of malignant cells in pleural or pericardial effusion
- •Serious uncontrolled systemic disorders (e.g., active infection, unstable cardiovascular disease)
- •Medical, psychological, or social conditions that could interfere with compliance
- •Active malignancy other than SCLC (except localized prostate/breast cancer or basal cell carcinoma)
- •Refusal or inability to sign informed consent
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From date of randomization until disease progression or death, whichever occurs first, assessed up to 5 years
Progression-Free Survival (PFS) is defined as the time from randomization to documented disease progression based on RECIST 1.1 criteria or death from any cause. Patients will be evaluated at baseline, every 3 months for the first 2 years, then every 6 months up to year 5 using imaging and clinical assessment.
次要结局
- Incidence of Acute and Late Toxicities (per CTCAE v4.0)(From treatment initiation through 5-year follow-up)
- Overall Survival (OS)(From date of randomization until death from any cause, assessed up to 5 years)
- Quality of Life Assessment (EORTC QLQ-C30)(Baseline, 3 months, 6 months, 12 months, and annually up to 5 years)
- Quality of life Assesment (LC13)(Baseline, 3 months, 6 months, 12 months, and annually up to 5 years)
- Quality of Life Assesment (LC29)(Baseline, 3 months, 6 months, 12 months, and annually up to 5 years)
- Time to First Local or Distant Recurrence(From randomization until first documented recurrence, assessed up to 5 years)