A Phase I Trial of an Immune Checkpoint Inhibitor Plus Stereotactic Ablative Radiotherapy in Patients With Inoperable Stage I Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose
研究概览
简要总结
This phase I trial studies the side effects and best dose of atezolizumab that can be given together with stereotactic body radiation therapy (SBRT) in treating patients with stage I non-small cell lung cancer that cannot be removed by surgery. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Stereotactic body radiation therapy is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Giving atezolizumab together with stereotactic body radiation therapy may kill more tumor cells and be a better treatment for non-small cell lung cancer that cannot be removed by surgery.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of MPDL3280A (atezolizumab) that can be given with stereotactic ablative radiotherapy (SAR) (stereotactic body radiation therapy) in patients with inoperable stage I non-small cell lung cancer (NSCLC).
SECONDARY OBJECTIVES:
I. To characterize the safety profile of this regimen using CTCAE v4 (Common Toxicity Criteria for Adverse Events version 4).
II. To provide preliminary efficacy data of the combination as determine by objective response rate and disease free survival using RECIST 1.1 (Response Evaluation Criteria for Solid Tumors) and Immune Related RECIST (irRECIST).
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 proven stage I NSCLC =< 5 cm diameter
- •One or more high-risk features identified:
- •Tumor diameter >= 2 cm
- •Tumor standardized uptake value maximum (SUVmax) >= 6.2
- •Moderately, poorly differentiated or undifferentiated histology
- •Evaluable disease per RECIST 1.1
- •Patients must be medically or surgically inoperable as determined by a physician OR unwilling to undergo surgical resection
- •All patients must have an forced expiratory volume in 1 second (FEV1) >= 700cc
- •All patients must have a carbon monoxide diffusing capability test (DLCO) >= 5.5 m/min/mmHg
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2
- •Life expectancy >= 12 months
- •Absolute neutrophil count (ANC) > 1500 cells/uL
- •White blood cell count (WBC) > 2500/uL
- •Lymphocyte count > 500/uL
- •Platelet count > 100,000/uL
- •Hemoglobin > 9 g/dL
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN) with alkaline phosphatase =< 2.5 x ULN OR AST and ALT =< 1.5 x ULN, with alkaline phosphatase > 2.5 x ULN
- •Serum bilirubin =< 1.0 x ULN
- •International normalized ratio (INR) and activated partial thromboplastin time (aPTT) < 1.5 x ULN (for patients on anticoagulation they must be receiving a stable dose for at least 1 week prior to enrollment)
- •Creatinine clearance > 30 mL/min by Cockcroft-Gault formula
- •No history of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)
- •No other active malignancy
- •Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible
- •Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible
- •Archival tumor sample available; tissue from an fine-needle aspiration (FNA) is allowed but tumor tissue from a core needle biopsy is preferred
- •For female patients of childbearing potential and male patients with partners of childbearing potential agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate [< 1% per year] when used consistently and correctly) and to continue its use for 6 months after the last dose of MPDL3280A
- •Signed informed consent
- •Ability to comply with the protocol
排除标准
- •Uncontrolled concomitant disease
- •Significant cardiovascular disease (New York Heart Association Class [NYHA] class II or greater); myocardial infarction within 3 month prior to randomization, unstable arrhythmias, unstable angina or a patient with a known left ventricular ejection fraction (LVEF) < 40%
- •Severe infection within 4 weeks prior to enrollment
- •Active tuberculosis
- •Oral or IV antibiotics within 2 weeks or 5 half-lives prior to enrollment
- •History of autoimmune disease
- •Positive for human immunodeficiency virus (HIV), hepatitis B (hepatitis B surface antigen [HBsAg] reactive), or hepatitis C virus (hepatitis C virus ribonucleic acid [HCV RNA] [qualitative] is detected)
- •History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia
- •Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrollment
- •Treatment with systemic corticosteroids or other systemic immunosuppressive medications within past 4 weeks or 5 half-lives whichever is shorter
- •Pregnant and/or lactating women
研究组 & 干预措施
atezolizumab + SBRT
DOSE ESCALATION PHASE: Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Within 24-48 hours after receiving atezolizumab, patients also undergo 4-5 fractions of stereotactic body radiation therapy over days 1-5 of course 3.
EXPANSION PHASE: Patients receive atezolizumab IV over 30-60 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Within 24-48 hours after receiving atezolizumab, patients also undergo 4-5 fractions of stereotactic body radiation therapy over days 1-5 of course 3.
干预措施: Atezolizumab (Drug)
atezolizumab + SBRT
DOSE ESCALATION PHASE: Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Within 24-48 hours after receiving atezolizumab, patients also undergo 4-5 fractions of stereotactic body radiation therapy over days 1-5 of course 3.
EXPANSION PHASE: Patients receive atezolizumab IV over 30-60 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Within 24-48 hours after receiving atezolizumab, patients also undergo 4-5 fractions of stereotactic body radiation therapy over days 1-5 of course 3.
干预措施: Stereotactic Body Radiation Therapy (Radiation)
结局指标
主要结局
Maximum Tolerated Dose
时间窗: 9 weeks
The adverse events will be summarized as frequency, proportion of patients MTD. The exact 95% confidence interval for proportion will be categorized by type, severity, nadir or maximum values for the laboratory measures, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities by dose and course.
次要结局
- Disease free survival (DFS), assessed by RECIST 1.1 and irRECIST(Up to 5 years)
- Overall response rate (ORR), assessed by RECIST 1.1(Time from the start of the treatment until disease progression/recurrence, assessed up to 5 years)
研究者
Megan Daly, MD
Principal Investigator
University of California, Davis