PRELUDE-1 (Prospective Evaluation of Radiotherapy-induced Biologic Effects in Colorectal Cancer Oligometastatic Patients with LUng-limited Disease: Evolution of Cancer Genetics and Regulatory Immune Cells)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- To assess the efficacy of SBRT in inducing a regressive genetic trajectory of KRAS gene (evaluated by NGS technique) after SBRT treatment.
研究概览
简要总结
PRELUDE-1 study is a pilot intervention trial that aims to describe the immunologic and genetic evolutions induced by stereotactic body radiationtherapy (SBRT) treatment in oligometastatic Colorectal Cancer (omCRC) patients with two-three nodules lung-limited disease.
详细描述
PRELUDE-1 study is a monocentric pilot interventional trial. The study concerns all patients enrolled with a diagnosis of oligometastatic Colorectal Cancer (omCRC) with two-three nodules lung-limited disease and treated with SBRT technique. SBRT will be delivered according to a risk-adapted protocol.
Tumor genetic background will be assessed on primary FFPE (Formalin Fixed Paraffin Embedded) tissues. Liquid biopsy will be done on blood samples collected before radiotherapy (RT) start and after 40 days to monitor tumor DNA evolution. The most direct method to assess cancer genetics relies on sampling of tumor DNA and its characterization through whole genome sequencing techniques (NGS, Next Generation Sequencing).
The study will last 48 months, divides as follow: 24 months of enrollment phase and up to 24 months of follow-up. Follow-up will be performed on the 40th day after the end of radiation treatment and then every 3 months until progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age <80 years
- •Cytological or histological diagnosis of colorectal adenocarcinoma
- •Two or three asymptomatic lung nodules smaller than 25 mm
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- •Available Formalin Fixed Paraffin Embedded (FFPE) of resected primary tumor
- •Negative pregnancy test for all potentially childbearing women
- •Patient candidates to SBRT
排除标准
- •Previous systemic anti-tumor treatments (allowed treatment with capecitabine or fluorouracil and radiotherapy in the neoadjuvant setting of rectal tumors with therapy terminated at least 6 months before)
- •Neutrophils <2000/mm³ or platelets <100.000/mm³ or hemoglobin <9 g/dl; serum creatinine level> 1.5 times the maximum normal value; GOT and/or GPT >5 times the maximum normal value and/or bilirubin level >3 times the maximum normal value
- •Previous or concomitant malignant neoplasms (excluding basal or spinocellular cutaneous carcinoma or in situ carcinoma of the uterine cervix)
- •Active or uncontrolled infections
- •Other concomitant uncontrolled diseases or conditions contraindicating the study drugs at clinician evaluation
- •Presence of brain metastases
- •Refusal or inability to provide informed consent
- •Impossibility to guarantee follow-up
研究组 & 干预措施
Liquid biopsy
Blood samples for liquid biopsy
干预措施: Stereotactic Body Radiation Therapy (SBRT) (Device)
结局指标
主要结局
To assess the efficacy of SBRT in inducing a regressive genetic trajectory of KRAS gene (evaluated by NGS technique) after SBRT treatment.
时间窗: 40 days after the end of RT
A genetic regressive trajectory is defined as KRAS mutated (any mutation) before SBRT and wild-type after SBRT (mutKRAS before SBRT→wtKRAS after SBRT). The sample size of the study is planned on this genetic trajectory, assuming a frequency of the phenomenon of 1/130 (as desumed from literature review). To be exhaustive, other realistic combinations are: wtKRAS→wtKRAS; mutKRAS→mutKRAS; wtKRAS→mutKRAS. Other assumptions for sample size calculation are: an alpha value of 0.05; a priori successful events rate of 0.077; 1-beta=0.60.
次要结局
- To evaluate the responses' duration (measured from the time of documented objective response until documented tumor progression).(Up to 24 months after the end of RT)
- To evaluate the response according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, version 1.1 including any eventual abscopal effect.(Up to 24 months after the end of RT)
- The toxicity, which will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute, version 5.0, November 27, 2017.(Up to 24 months after the end of RT)
- Tumor immune microenvironment in primary tumour(40 days after the end of RT)
- Metabolic response (exploratory studies)(40 days after the end of RT)
- To evaluate the progression-free (PFS) survival (from the data of treatment start untill progression).(Up to 24 months after the end of RT)