Phase I/II Study of the Safety, Tolerability, and Efficacy of Stereotactic Body Radiation Therapy (SBRT) Combined With Concurrent and Adjuvant Avelumab for Definitive Management of Early Stage Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Adverse Events
研究概览
简要总结
The purpose of the study is to determine whether avelumab has an effect on cancer and body in combination with SBRT, a standard treatment for early stage non-small cell lung cancer (NSCLC).
Avelumab is considered experimental because it is not approved by the United States (U.S.) Food and Drug Administration (FDA) for the treatment of cancer. It is a type of drug called a monoclonal antibody (a type of protein). Monoclonal antibodies are made to recognize, target and bind to specific proteins on the cells that make up your tissues. Avelumab is designed to block the interaction between PD-1, a known immune checkpoint, and PD-L1. By blocking this interaction, the immune system may be stimulated, allowing it to more effectively recognize and attack the cancer.
Stereotactic Body Radiation Therapy (SBRT) is a type of radiation that uses precise targeting to deliver a high dose of radiation to the tumor over a short period of time. A positioning cushion such as Vac-lok will be used during radiation treatment that is custom made. This custom mold forms to the contours of the subjects body to allow for proper positioning comfort and stability.
详细描述
This is a single arm open label Phase I/II study that will consist of two parts. In Phase I, investigators will assess the safety and tolerability of SBRT combined with Avelumab. In Phase II, investigators will determine whether SBRT combined with Avelumab improves relapse free survival. Subjects with Stage I NSCLC who are not undergoing surgical resection will be candidates for enrollment. Subjects will receive definitive stereotactic body radiation (SBRT) in 4-5 fractions combined with concurrent and adjuvant Avelumab at 10mg/kg for a total of 6 cycles. Subjects will be evaluated for safety as measured by the occurrence of adverse events, serious adverse events, and laboratory abnormalities. Three blood draws will be obtained to analyze anti-tumor immune responses and immune correlates.
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
- •Tumor(s) to be treated is(are) ≤ 5.0 cm or ≤250 cm3
- •Stage I NSCLC and is deemed medically inoperable or refuses surgical resection.
- •Life expectancy ≥ 9 months.
- •Acceptable organ and marrow function
排除标准
- •Prior organ transplantation, including allogeneic stem cell transplantation
- •Significant acute or chronic infections including:
- •Known history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- •Known history of HBV or HCV
- •Active autoimmune disease
- •Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
- •Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day
- •Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable
- •Current use of immunosuppressive medication, EXCEPT for the following:
- •intranasal, inhaled, topical steroids, or local steroid injection (eg, intra-articular injection)
- •Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent
- •Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
- •Cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure, or serious cardiac arrhythmia requiring medication.
- •Known severe hypersensitivity reactions to monoclonal antibodies any history of anaphylaxis, or uncontrolled asthma
- •Pregnancy or lactation
- •Known alcohol or drug abuse
- •Prior radiotherapy to the treatment site(s).
研究组 & 干预措施
SBRT+Avelumab
SBRT: 12Gy x 4 fractions or 10Gy x 5 fractions (4-5 radiation doses given over 10-12 days every other day.)
Avelumab 10mg/kg IV infusion every 2 weeks for 6 cycles
干预措施: Avelumab (Drug)
SBRT+Avelumab
SBRT: 12Gy x 4 fractions or 10Gy x 5 fractions (4-5 radiation doses given over 10-12 days every other day.)
Avelumab 10mg/kg IV infusion every 2 weeks for 6 cycles
干预措施: SBRT (Radiation)
结局指标
主要结局
Adverse Events
时间窗: 6 months
Safety and tolerability of definitive SBRT combined with concurrent and adjuvant Avelumab in patients with early stage NSCLC (Measured Via Adverse Events).
Relapse Free Survival (RFS)
时间窗: 3 years
Relapse-Free Survival (RFS) is defined as the time from starting treatment to the time of first documented tumor progression or death due to any cause, whichever occurs first. Death is considered as an event here.
次要结局
- Loco-regional Control (LRC)(3 years)
- Overall Survival in Patients After Completion of SBRT in Combination With Avelumab(3 years)
研究者
Andrew Sharabi
Assistant Clinical Professor
University of California, San Diego