Combining an Immune Checkpoint Inhibitor With SBRT or Hypo-fractionated RT in the Treatment of Stage I-III NSCLC: an Exploratory Study on Radiation Dose and Treatment Efficacy.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 83
- 试验地点
- 1
- 主要终点
- The incidence of any adverse events that is >= grade 3
研究概览
简要总结
This study will explore the best dose of radiation to be used when treating stage I-III non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) or hypo-fractionated radiotherapy (HypoFrx-RT) that is delivered in combination with an immune checkpoint inhibitor. Treatments with SBRT or HypoFrx-RT for locally confined NSCLC show positive response which may be further augmented when they are combined with an immune checkpoint inhibitor. Currently, it is not understood what radiation dose is most suitable for such combined treatments and their clinical efficacy in the treatment of early stage (ES) NSCLC. Therefore, this study can help researchers gain insight into what a safe and effective SBRT or HypoFrx-RT dose will be when such radiotherapeutic approaches are combined with concurrent and adjuvant administration of an immune checkpoint inhibitor in the treatment of ES NSCLC.
详细描述
Patients will be assigned to Cohort A or Cohort B based on tumor stage (AJCC 8th Ed.).
Cohort A: cT1-T3, N0, M0 (selected cT1, No, M0)
Cohort B: cT4, N0, M0; cT1-4, N1-3, M0
Phase I:
This portion of the study will utilize a standard 3 + 3 phase I design with three patients enrolled per radiation dose level in each cohort. Enrollment in the two cohorts is independent from one another. In both cohorts, an anti-PD-(L)1 immune checkpoint inhibitor will be given concurrently and adjuvantly with radiotherapy for approximately 1 year.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- 是
入选标准
- •Key Inclusion Criteria
- •Informed Consent
- •Stage I-III NSCLC per AJCC 8th. ed.
- •Tumor PD-L1 expression ≥1% preferred
- •Tumor sample submission
- •Tumor staging prior to registration
- •Age ≥ 18 years
- •WHO/ECOG PS of 0, 1, or 2
- •Life expectancy ≥12 weeks
- •Adequate organ or bone marrow function
- •Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.
排除标准
- •Key Exclusion Criteria
- •Mixed small cell and non-small cell lung cancer histology
- •Definitive clinical or radiologic evidence of metastatic disease
- •Patients who received systemic therapy for the current cancer prior to enrollment
- •Thoracic radiotherapy within 5 years with exceptions
- •Major surgery within 28 days prior to enrollment with exception
- •Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
- •History of another primary malignancy with exceptions
- •History of idiopathic pulmonary fibrosis, any pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on chest PET/CT or CT scan
- •Active or prior documented autoimmune disease with exceptions
- •History of primary immunodeficiency
- •History of allogenic organ or tissue transplantation
研究组 & 干预措施
Cohort A
SBRT to be delivered with concurrent and adjuvant anti-PD-(L)1 immune checkpoint inhibitor.
干预措施: Stereotactic body radiotherapy (Radiation)
Cohort A
SBRT to be delivered with concurrent and adjuvant anti-PD-(L)1 immune checkpoint inhibitor.
干预措施: Durvalumab (Drug)
Cohort B
Hypo-fractionated radiotherapy to be delivered with concurrent and adjuvant anti-PD-(L)1 immune checkpoint inhibitor.
干预措施: Hypofractionated radiotherapy (Radiation)
Cohort B
Hypo-fractionated radiotherapy to be delivered with concurrent and adjuvant anti-PD-(L)1 immune checkpoint inhibitor.
干预措施: Durvalumab (Drug)
结局指标
主要结局
The incidence of any adverse events that is >= grade 3
时间窗: 2 years
Adverse events will be graded according to CTCAE v.5.0
Progression-free survival (PFS)
时间窗: 2 years
PFS is defined as free from any disease progression or death after combined treatment for NSCLC.
Maximum tolerated dose (MTD)
时间窗: 2 years
MTD in cohort A and cohort B, respectively.
次要结局
- Quality of Life (QoL), Lung cancer specific(2 years)
- Overall survival (OS)(2 years)
- Local control(2 years)
- Quality of Life (QoL)(2 years)
研究者
Alexander Chi
Professor
Xuanwu Hospital, Beijing