Nivolumab and Ablation For Patients With Advanced Non-Small Cell Lung Cancer Progressing After at Least One Prior Therapy For Metastatic Disease: A Brown University Oncology Research Group Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Response Rate of the Combination of Ablation and the PD-1 Inhibitor Nivolumab for Patients With Non-small Cell Lung Cancer (NSCLC) Who Have Progressed Following at Least 1 Prior Chemotherapy Regimen for Metastatic or Locally Advanced Disease.
研究概览
简要总结
Nivolumab releases the inhibition of the immune system against human cancers. Dramatic and sustained activity has been observed in advanced lung cancer. Ablation may stimulate the immune system by exposing new tumor antigens. Since tumors that express PD-L1 may be more likely to respond to nivolumab, if ablation increases PD-L1 expression (which has not been studied) this treatment may enhance the activity of nivolumab at both the treated site and in other, non-treated, tumors. Ablation is already an FDA approved treatment for cancer. Nivolumab was recently FDA approved for second line treatment of advanced squamous cell NSCLC. The goal of the study will be to determine if the combination of nivolumab and ablation has higher systemic activity than previously reported with nivolumab alone.
详细描述
See summary above
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
- •Pathologically or cytologically confirmed NSCLC
- •Stage IIIB or stage IV.
- •Patient to meet either criterion A or B:
- •A) Progression after at least 1 line of systemic treatment (IV or oral) for metastatic or locally advanced disease. Must provide documentation systemic treatment was for either locally advanced or metastatic and also scan or assessment to show progression. Radiation does not count as 1 line.
- •B) Patients progressing within 6 months of completion of neoadjuvant or adjuvant chemotherapy are also eligible without having treatment for metastatic disease (for example patient with stage I disease undergoes resection, receives systemic chemotherapy and then progresses to the liver (now stage IV) within 6 months of chemotherapy). Radiation does not count as 1 line.
- •Ablation for advanced lung cancer is being considered by the treating physician for treatment or prevention of symptoms such as pain, bleeding or obstruction- Documentation is required in writing by MD for this criterion.
- •At least 1 site of measurable disease that will not be treated with ablation. Sites to send confirmation on which lesion of measurable disease will not be ablated for tracking of response.
- •At least 3 weeks since prior chemotherapy and radiation therapy
- •No brain metastases except for patients whose metastases have been removed by surgical resection or have had stereotactic radiation or gamma knife with no evidence of active disease on MRI within 28 days of starting treatment.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-
- •Life expectancy of at least 12 weeks.
- •Required entry laboratory parameters within 14 days of study entry: Granulocytes ≥ 1000/µl; platelet count ≥75,000/µl; absolute lymphocyte count ≥ 500/ µl; Creatinine ≤ 1.5x upper limit normal mg/dl; Bilirubin < 1.5x upper limit normal; AST ≤ 3 x upper limit of normal.
- •Age > 18 years
- •Men and women of childbearing potential enrolled in this study must agree to use adequate barrier birth control measures during the course of the study and up to 2 months after.
- •Written informed consent.
排除标准
- •Patients with a history of clinically significant chronic autoimmune disease
- •Prior therapy with antibodies that modulate T-cell function defined as anti-CTLA-4, anti-PD-1, and anti-PD-L1
- •Conditions currently requiring immunosuppressive medications
- •Known history of HIV or hepatitis B or C
- •Bleeding diathesis or coagulopathy that in the investigators opinion would prevent ablation from being safely performed.
- •Patients with unstable angina (anginal symptoms at rest) or new-onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- •History of organ allograft even if not taking immunosuppressive medications
- •Pregnant or breast-feeding.
研究组 & 干预措施
Nivolumab with ablation
3mg/kg IV over 60 minutes on Day 1 +/- 3 days every 2 weeks until progression for a maximum of 2 years.
Either cryoablation or thermal ablation may be performed as per standard institutional policies.
As of amendment # 7 submitted to sites November 17, 2017, the dosing for Nivolumab per the FDA guidance was amended to a flat dose of 240mg IV Q2 weeks. As of amendment #8 sent to sites February 22, 2017 the dose of Nivolumab was updated to 3 mg/kg with a maximum dose of 240 mg for patients with weights that would correlate to exceed that dose instead of a flat dose secondary to the standard institutional practice and the FDA guidance .
干预措施: nivolumab and ablation (Drug)
结局指标
主要结局
Response Rate of the Combination of Ablation and the PD-1 Inhibitor Nivolumab for Patients With Non-small Cell Lung Cancer (NSCLC) Who Have Progressed Following at Least 1 Prior Chemotherapy Regimen for Metastatic or Locally Advanced Disease.
时间窗: Up to 5 years.
Assessment of tumor response by scan 12 weeks post the first dose of Nivolumab and approximately every 12 weeks after. Post progression by RECIST a 1 month confirmatory scan will be done and that will be the indicator of Progression.
次要结局
未报告次要终点
研究者
howard safran
Prinicipal Investigator
Brown University