CHEckpoint Inhibition in Combination With an Immunoboost of External Beam Radiotherapy in Solid Tumors: CHEERS-trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 99
- 试验地点
- 4
- 主要终点
- Progression-free survival
研究概览
简要总结
This randomized controlled phase II trial will investigate whether the addition of stereotactic body radiotherapy to checkpoint inhibitor treatment in patients with non-small-cell lung carcinoma, urothelial carcinoma, renal cell carcinoma, melanoma or head-and-neck carcinoma can improve progression-free survival as compared to checkpoint inhibitor monotherapy. The primary outcome is progression-free survival; secondary outcomes include overall survival, response according to iRecist and Recist v1.1 and toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- 否
入选标准
- •Before patient registration, written informed consent must be given according to ICH/GCP and national/local regulations.
- •Histologically confirmed diagnosis of a solid tumour.
- •At least one extracranial tumour lesion available for radiotherapy administration.
- •Patient will receive a checkpoint inhibitor per standard of care in one of the following settings (locally advanced or metastatic): melanoma (1st - 3rd line nivolumab or pembrolizumab); renal cell carcinoma (2nd line nivolumab); non-small cell lung carcinoma (2nd or 3rd line nivolumab, pembrolizumab or atezolizumab); urothelial cell carcinoma ( 1st-3rd line nivolumab, pembrolizumab or atezolizumab); head-& neck squamous cell carcinoma (1st-2nd line pembrolizumab, 2nd line nivolumab).
- •Karnofsky Performance status >
- •Age 18 years or older.
排除标准
- •Prior radiotherapy preventing treatment with SBRT.
- •Prior treatment with an anti-PD-(L)1 antibody.
- •Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or prostate cancer that has undergone potentially curative therapy and with normalized PSA.
- •Uncontrolled central nervous system (CNS) metastases at baseline (controlled = previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants), and/or carcinomatous meningitis.
- •Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medication within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
- •Has a diagnosis of immunodeficiency or history of human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection.
- •Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study.
- •Patient not likely to comply with the protocol; I.e. uncooperative attitude, inability to return for follow-up visits and unlikely to complete the study.
- •Contraindication for radiotherapy.
- •Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
研究组 & 干预措施
Experimental arm
Stereotactic body radiotherapy concurrent with checkpoint inhibitor treatment:
Nivolumab or Pembrolizumab or Atezolizumab + SBRT
干预措施: Nivolumab or Pembrolizumab or Atezolizumab (Drug)
Experimental arm
Stereotactic body radiotherapy concurrent with checkpoint inhibitor treatment:
Nivolumab or Pembrolizumab or Atezolizumab + SBRT
干预措施: SBRT (Radiation)
Control arm
Checkpoint inhibitor treatment only:
Nivolumab or Pembrolizumab or Atezolizumab monotherapy
干预措施: Nivolumab or Pembrolizumab or Atezolizumab (Drug)
结局指标
主要结局
Progression-free survival
时间窗: 15 months
Progression-free survival will be defined as the time from randomization to disease progression (as per iRECIST) or death from any cause.
次要结局
- Overall survival(2 years after start trial treatment)
- Tumor response as per iRECIST(12 weeks)
- Tumor response as per RECIST(12 weeks)
- Incidence of Treatment-Related Adverse Events [safety and tolerability](12 weeks)
- Patient-reported quality of life(12 weeks)
- Systemic immune response(12 weeks)