A Real-world Study to Explore and Evaluate Individualized Targeted Agents for Patients of Digestive Cancers Based on Molecular Characteristics After Standard Therapy Failure in China
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 600
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR) of patients receiving targeted agent
研究概览
简要总结
This a prospective real-world navigation study using tumor DNA sequencing technology to sequence genes of previously treated and refractory gastrointestinal tumors, which are generally considered to be highly heterogeneous and complex, to screen potential molecular targeted drugs for individualized treatment. This study may provide feasibility and response information, which will be the basis for designing better randomized trials, which may change the pattern of cancer treatment. If the hypothesis is finally proved, it will help doctors and molecular biologists to choose the best drug (or combination of drugs) based on the individual oncogenomics of each patient.
详细描述
This is a prospective, open label, real-world study to evaluate the feasibility of matched molecular targeted therapy in patients with refractory gastrointestinal cancer based on tumor molecular characteristics as standard treatment failure. This is a non-randomized trial designed to test molecular matching strategies based on patient genome information. The molecular tumor board (MTB) will recommend treatment, but the treatment decision is up to the attending physician. FoundationOne CDx was used for tissue genomic analysis. If possible, PD-L1 immunohistochemistry (IHC), tumor mutation load (TMB), and microsatellite instability (MSI) status will also be evaluated. Based on this information, MTB, composed of multidisciplinary experts, will focus on the selection of customized, best matched drugs or combinations to target most of the genomic changes in each patient, also taking into account potential drug toxicity. The final treatment will be based on the choice of oncologists, who will formulate treatment plan by combining MTB discussion, patient preference, attention to complications, consideration of drug toxicity, insurance coverage of off label drugs and availability of clinical trials of research drugs, thus reflecting the actual clinical practice nowadays in China. The acquisition of drugs follows the actual situation in the real world and is not within the scope of this study design.
The principles of MTB treatment recommendations can be referred to the NCI-MATCH trial:
Grade 1: FDA / NMPA approval; clear evidence and mechanism; concomitant diagnostic relationship between drug and target.
Grade 2: The drug reaches the clinical end point (objective response rate, PFS or OS); there is evidence of target inhibition; there is strong evidence to predict relationship between the target and the drug.
Grade 3: The drug has evidence of clinical activity and target inhibition; there is some evidence to predict the relationship between target and drug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Histologically confirmed recurrent or metastatic malignant tumors of digestive tract, including but not limited to:
- •Biliary tract cancer (including gallbladder cancer and cholangiocarcinoma)
- •Gastric cancer
- •Esophageal squamous cell carcinoma
- •Colorectal cancer
- •Gastrointestinal stromal tumor
- •Pancreatic cancer
- •Primary unknown metastatic carcinoma of digestive system
- •failure of conventional treatment;
- •have at least one measurable lesion according to RESIST1.1;
- •the target lesion is not suitable for local treatment;
- •the expected survival time was more than 3 months;
- •age ≥ 18 years old;
- •the main organs function well;
- •be able to swallow and retain oral medication if necessary;
- •patients must have enough tissue samples for gene mutation detection;
- •informed consent signed.
排除标准
- •main lesions were suitable for local treatment;
- •serious or uncontrolled medical diseases that researchers consider to be confusing in the treatment response analysis (i.e. uncontrolled diabetes, chronic kidney disease, chronic lung disease or uncontrolled active infection, mental illness / social status that limits compliance with research requirements);
- •pregnant or lactating patients or any fertile patients taking no appropriate pregnancy prevention.
研究组 & 干预措施
Unmatched Therapy
Unmatched Therapy
干预措施: Other Therapy (Drug)
Matched Targeted Agent
Matched Targeted Agent
干预措施: FGFR Inhibitor, IDH1 Inhibitor, HER2 Inhibitor, PARP Inhibitor, BRAF Inhibitor, MEK Inhibitor, ICIs, EGFR-TKIs, NTRK-TKI, and et. al. (Drug)
结局指标
主要结局
Objective response rate (ORR) of patients receiving targeted agent
时间窗: up to 2 years
Objective response rate (ORR) per RECIST 1.1 criteria according to investigators assessment
次要结局
- Proportion of patients with intervening genomic variation(up to 2 years)
- Differences of OS between 2 groups(up to 2 years)
- Progression Free Survival (PFS) of patients receiving targeted agent(up to 2 years)
- Overall Survival (OS) of patients receiving targeted agent(up to 2 years)
- Number of participants with treatment-related adverse events(up to 2 years)
研究者
Shen Lin
Professor
Peking University