Fraction Dose Escalation of Hypofractionated Radiotherapy With Concurrent Chemotherapy and Subsequent Consolidation Immunotherapy in Locally Advanced Non-small Cell Lung Cancer: a Phase 1 Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- the maximally tolerated fraction dose
研究概览
简要总结
This Phase 1 trial aimed to determine the maximum tolerated fraction dose (MTD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer (LA-NSCLC).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non-small cell lung cancer confirmed by histology.
- •Tumor size is measured according to RECIST standard.
- •Unresectable stage IIIA (N2) and IIIB/IIIC, confirmed by PET-CT/or chest and abdomen CT, brain MRI, and whole body bone scan.
- •18-75 years old, regardless of gender.
- •The ECOG score is 0-
- •Newly treated or underwent neoadjuvant chemotherapy and/or immunotherapy.
- •Have not received chest radiotherapy in the past.
- •Serum hemoglobin ≥10 mg/dL, platelets ≥100000/μL, absolute neutrophil count ≥1500/μL.
- •Serum creatinine ≤1.25 times UNL or creatinine clearance ≥60 ml/min.
- •Serum bilirubin ≤1.5 times UNL, AST (SGOT) and ALT (SGPT) ≤2.5 times UNL, alkaline phosphatase≤ 5 times UNL.
- •FEV1>1 L.
- •CB6 normal range.
- •The patient and his family members agree and sign an informed consent form.
排除标准
- •Other malignant tumors in the past or during treatment, except for non-melanoma of the skin or carcinoma in situ of the cervix.
- •Any other diseases or conditions are contraindications to chemotherapy (such as active infection, within 6 months after myocardial infarction, symptomatic heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmia, immunosuppressive therapy).
- •Pregnant or breastfeeding women, women who have not undergone a pregnancy test (within 14 days before the first dose), and pregnant women.
- •Those who are pregnant, breastfeeding or have fertility but have not taken contraceptive measures.
- •People with bleeding tendency.
- •Those who participated in other clinical trials within 30 days before participating in this experiment.
- •Drug addiction, long-term alcoholism, and AIDS patients.
- •People with uncontrollable seizures or loss of self-control due to mental illness.
- •People with a history of severe allergies or specific physique.
- •The researcher believes that the patient is inappropriate to participate in this trial.
- •Exit criteria
- •The treatment cannot be carried out in accordance with the requirements of the research protocol;
- •The patient has an allergic reaction ≥ grade 4 or a serious adverse reaction to the study drug;
- •The patient is pregnant or has not used adequate contraceptive measures;
- •The researcher judges that the patient should not continue to participate the clinical trial;
- •The subject asked to withdraw.
研究组 & 干预措施
Split-course adaptive HRT-CHT
In keeping the same total radiation dose (60Gy), we escalate the fraction dose to find the maximum tolerable fraction dose.
- Level 1: DT 4500cGy/15 daily fractions/300cGy in the first course，DT 1500cGy/5 daily fractions/300cGy in the second course;
- Level 2: DT 4000cGy/10 daily fractions/400cGy in the first course， DT 2000cGy/5 daily fractions/400cGy in the second course;
- Level 3: DT 3000cGy/6 daily fractions/500cGy in the first course， DT 3000cGy/6 daily fractions/500cGy in the second course.
RT is delivered using the IMRT technique with daily cone-beam CT image guidance. The dose limitation of organ at risk (OAR) are shown in Table 1. Patients receive a weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT. Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT.
干预措施: Hypofractionated radiotherapy (Radiation)
Split-course adaptive HRT-CHT
In keeping the same total radiation dose (60Gy), we escalate the fraction dose to find the maximum tolerable fraction dose.
- Level 1: DT 4500cGy/15 daily fractions/300cGy in the first course，DT 1500cGy/5 daily fractions/300cGy in the second course;
- Level 2: DT 4000cGy/10 daily fractions/400cGy in the first course， DT 2000cGy/5 daily fractions/400cGy in the second course;
- Level 3: DT 3000cGy/6 daily fractions/500cGy in the first course， DT 3000cGy/6 daily fractions/500cGy in the second course.
RT is delivered using the IMRT technique with daily cone-beam CT image guidance. The dose limitation of organ at risk (OAR) are shown in Table 1. Patients receive a weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT. Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT.
干预措施: Concurrent chemotherapy (Drug)
Split-course adaptive HRT-CHT
In keeping the same total radiation dose (60Gy), we escalate the fraction dose to find the maximum tolerable fraction dose.
- Level 1: DT 4500cGy/15 daily fractions/300cGy in the first course，DT 1500cGy/5 daily fractions/300cGy in the second course;
- Level 2: DT 4000cGy/10 daily fractions/400cGy in the first course， DT 2000cGy/5 daily fractions/400cGy in the second course;
- Level 3: DT 3000cGy/6 daily fractions/500cGy in the first course， DT 3000cGy/6 daily fractions/500cGy in the second course.
RT is delivered using the IMRT technique with daily cone-beam CT image guidance. The dose limitation of organ at risk (OAR) are shown in Table 1. Patients receive a weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT. Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT.
干预措施: Consolidation immunotherapy (Drug)
结局指标
主要结局
the maximally tolerated fraction dose
时间窗: 1 year
The maximum tolerated fraction dose was defined as the highest DL in which \<=2 patients of the 6 treated patients experienced G3+ toxicity and \<=1 patient experienced G4+ toxicity within 12 months after RT. If a patient had multiple types of toxicities, only the highest grade of toxicity was counted.
次要结局
- Overall survival(1-year)
- Objective response rate(2 months after radiotherapy)
- Progression-free survival(1-year)
- Distant-metastasis free survival(1-year)
- Loco-regional recurrence-free survival(1-year)
研究者
Hui Liu
Professor
Sun Yat-sen University