Observational Study on the Abscopal Efect by Ultra-hypofractionated Radiation Therapyin Combination With Immune Checkpoint Inhibiters for Metastatic Renal Cell Carcinoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 145
- 试验地点
- 1
- 主要终点
- Abscopal Response Rate (ARR) at 1 Year After IGU
研究概览
简要总结
The goal of this multicenter observational study is to elucidate the clinical and immunological characteristics of the abscopal effect in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitors (ICI) combined with image-guided ultra-hypofractionated radiotherapy (IGU).
The main questions this study aims to answer are:
What is the abscopal response rate (ARR) at one year after IGU in patients continuing ICI treatment?
What clinical and immunological factors are associated with the occurrence and timing of the abscopal effect?
Participants are patients with mRCC who have experienced immune-confirmed stable or progressive disease during ICI therapy and are scheduled to receive IGU to a selected lesion. Researchers will observe tumor responses at irradiated and non-irradiated sites using standard imaging (CT/MRI) and collect clinical and laboratory data at baseline, 3, 6, 9, and 12 months after IGU. Optional exploratory blood samples will be obtained for cytokine analysis (e.g., IFN-β, IFN-γ, TNF-α, IL-6).
The primary outcome is the abscopal response rate (ARR) at one year after IGU. Secondary outcomes include tumor shrinkage rate of irradiated and non-irradiated lesions, 1-year overall survival, disease-specific survival, and progression-free survival.
This study seeks to establish a foundation for developing combined immunotherapy and ultra-hypofractionated radiotherapy strategies for metastatic renal cell carcinoma.
*This study is led by Prof. Hiroshi Onishi (University of Yamanashi). The registry entry is managed by Dr. Zhe Chen on behalf of the study group.
详细描述
Renal cell carcinoma (RCC) is a highly immunogenic tumor that exhibits intrinsic resistance to cytotoxic chemotherapy and conventional radiotherapy. With the introduction of immune checkpoint inhibitors (ICIs), such as nivolumab and ipilimumab, the survival outcomes of patients with metastatic RCC (mRCC) have markedly improved. However, disease control remains suboptimal in a considerable fraction of patients who experience immune-confirmed stable disease or progression despite continued ICI therapy. For such patients, locoregional treatment targeting oligoprogressive lesions may modulate tumor immunogenicity and enhance systemic immune responses.
Radiation therapy, particularly when administered in large doses per fraction (ablative or ultra-hypofractionated schedules), can induce systemic antitumor effects mediated by immune activation, known as the abscopal effect. This effect refers to regression of non-irradiated metastatic lesions following local irradiation, thought to arise from radiation-induced antigen release and subsequent immune activation. Although multiple case reports and small series have described this phenomenon, the true frequency, biological basis, and predictive factors of the abscopal effect in mRCC remain poorly defined.
The AURICRE study (Observational Study on the Abscopal Effect by Ultra-Hypofractionated Radiation Therapy in Combination with Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma) is a multicenter prospective observational registry initiated by the Department of Imaging-Integrative Therapeutic Radiology, University of Yamanashi. The study is designed to clarify the incidence, timing, and clinical-immunological correlates of the abscopal effect in patients with mRCC treated with ICIs who undergo ultra-hypofractionated image-guided radiotherapy (IGU) to a metastatic lesion. This investigation will also provide a foundation for the rational development of future ICI-radiotherapy combination strategies.
Study Objectives
Primary Objective To elucidate the clinical and immunological characteristics associated with the abscopal effect in mRCC patients receiving ICIs and to determine the abscopal response rate (ARR) at one year after IGU.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Patients aged 18 years and above with metastatic renal cell carcinoma
- •Patients currently receiving immune checkpoint inhibitor (ICI) therapy who are assessed as having iCPD or iSD according to iRECIST
- •Presence of two or more clinically measurable lesions (assessed by CT, MRI, physical examination, or visual inspection) Note: Osteosclerotic lesions without measurable soft-tissue components are excluded
- •Planned to undergo IGU to the target lesion
- •Provided written informed consent after receiving sufficient explanation of this study Note: Proxy signature is permitted if the patient is physically unable to sign
排除标准
- •Patients with active double cancers (synchronous double cancers or metachronous double cancers with a disease-free interval within 2 years).
- •However, carcinoma in situ or intramucosal carcinoma considered cured by treatment, and the following tumors even if within 2 years of disease-free interval are not excluded: gastric cancer stage 0-II (UICC), prostate cancer stage I-III, colorectal cancer stage 0-II, esophageal cancer stage 0-I, breast cancer stage 0-II, endometrial cancer stage I-II, cervical cancer stage 0-II, and thyroid cancer stage I-III. In addition, any cancer with a disease-free interval greater than 2 years is not excluded regardless of stage.
- •Patients with serious comorbidities, such as:
- •severe cardiac disease
- •uncontrolled diabetes mellitus despite continuous insulin therapy
- •myocardial infarction within 6 months
- •uncontrolled hypertension
- •active infections (bacterial, viral, or fungal)
- •diarrhea (watery stool), paralytic ileus, or bowel obstruction
- •autoimmune disease
- •any other severe comorbid condition
- •Patients with clear evidence of idiopathic interstitial pneumonia (usual interstitial pneumonia pattern) on chest X-ray or CT
- •Patients with acute-phase pneumonia
- •Patients with psychiatric disorders or psychiatric symptoms judged to make study participation difficult
结局指标
主要结局
Abscopal Response Rate (ARR) at 1 Year After IGU
时间窗: 12 months after image-guided ultra-hypofractionated radiotherapy (IGU)
The proportion of patients showing an abscopal response, defined as a ≥30% reduction in the sum of diameters of non-irradiated target lesions without new lesion appearance, evaluated according to RECIST 1.1 criteria. Tumor response will be assessed by radiological imaging (CT or MRI) at each follow-up visit and confirmed by central review.
次要结局
- Tumor Shrinkage Rate of Irradiated and Non-Irradiated Lesions(Baseline to 12 months after IGU)
- One-Year Overall Survival (OS)(12 months after IGU)
- One-Year Disease-Specific Survival (DSS)(12 months after IGU)
- One-Year Progression-Free Survival (PFS)(12 months after IGU)
研究者
Zhe Chen
Lecturer
University of Yamanashi