A Prospective Trail of Immunotherapy and Stereotactic Body Radiotherapy (SBRT) for the Treatment of Metastatic Lung Cancer: SBRT Sensitization of the Programmed Death-1 (PD-1) Effect
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Acute Toxicity: Radiation pnuemonitis measured using NCI CTCAE version 4.0
研究概览
简要总结
The purpose of this study is to determine efficacy, safety of Stereotactic Body Radiotherapy (SBRT) in combination with immunotherapy in participants with metastatic non-small cell lung cancer (NSCLC) who are eligible for an immunotherapy agent.
详细描述
Blockade of the PD-1/PD-L1 T-cell checkpoint pathway is an effective and well tolerated approach to stimulating the immune response which is a critical option in the treatment of metastatic NSCLC. However, progression free survival (PFS) is increased by only 2-4 months and median overall survival (OS) by 3-9 months.
There is compelling evidence that PFS is increased up to 3 fold and OS by 2 fold in patients receiving a course of radiation therapy while on immunotherapy. Radiotherapy is known to induce immunogenic tumor cell death and upregulation of dendritic cells and antigen presentation leading to activation of cytotoxic T-Cells. Dramatic T-cell activation has been demonstrated where tumor regression occurs outside the radiation treatment field in a phenomenon termed the abscopal effect and is associated with high dose radiation delivered via SBRT.
As such, SBRT activation of T-cells could be complementary to immunotherapy and enhance T-cell mediated killing via PD-L1 blockade which could lead to lasting and durable tumor response with improved progression free survival and overall survival.
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 or cytologically confirmed Stage IV NSCLC according to the 7th AJCC staging manual.
- •Eligible for an immunotherapy agent. Patients who progress after drug therapy (3 months) for ALK, EGFR or ROS mutation positive lung cancer are eligible.
- •At least 2 lesions that are safely amenable to SBRT. ECOG <=
- •At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for response assessment or at least 1 lesion with FDG avidity and CT correlate that can be monitored for PET-CT response by SUV Max increase or decrease.
- •Normal Hepatic and renal function.
- •Bone marrow reserve:
- •ANC ≥ 1.5 x 109/L
- •Hemoglobin ≥9.0 g/dL
- •Platelet count ≥75 x 109/L
- •Ability to comply with follow-up visits and evaluations, treatment planning and studies and other study related procedures and visits.
- •Ability to sign informed consent.
排除标准
- •Patients with active CNS metastases
- •Active, known or suspected auto-immune disease.
- •Patients with medical conditions that require systemic immunosuppression.
- •Patients with a history of interstitial lung disease.
- •Prior treatment with immune checkpoint inhibitors/immonotherapy.
- •Other active malignancy requiring intervention.
- •Prior lung radiation, with the only metastatic targets in the lungs.
- •Unresolved toxicity from prior chemotherapy or anti-cancer treatment.
- •Current or prior enrollment in clinical trial with an investigational drug within 4 weeks.
- •Pregnancy or positive pregnancy test.
结局指标
主要结局
Acute Toxicity: Radiation pnuemonitis measured using NCI CTCAE version 4.0
时间窗: 0-15 weeks
Determine excess/unexpected toxicity that cannot be attributed to routine radiation therapy or immunotherapy side effects.
Overall Survival
时间窗: 24 months
Determine overall survival in patients receiving SBRT and immunotherapy as compared to landmark trials of patients receiving immunotherapy alone (Checkmate 057, Keynote 024)
次要结局
- Local Control(0-24 Months)
- Impact of Tumor Burden(24 Months)
- Late Toxicity: Pulmonary, Bone or Visceral organ toxicity evaluated 6 months from completion of treatment using NCI CTCAE version 4.(6-24 Months)
- Progression Free Survival(3-24 Months)
研究者
Rachelle Lanciano M.D.
Principal Investigator
Crozer-Keystone Health System