A Non-interventional Uncontrolled Multicenter Study to Investigate the Emergence of RAS Resistance Mutations in RAS Wild Type mCRC Patients Receiving First Line Cetuximab Treatment
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 120
- 试验地点
- 4
- 主要终点
- Percentage of detected circulating DNA RAS mutations during 1st line cetuximab exposure.
研究概览
简要总结
To evaluate the emergence of RAS mutation in patients with metastatic colorectal cancer, circulating free DNA will be analyzed using mass spectrometric genotyping in subjects during cetuximab treatment. The hypothesis of this study is that acquired RAS mutation is responsible for the resistance to cetuximab treatment in wild-type colorectal cancer. The usefulness of liquid biopsy to monitor dynamic genetic alterations in colorectal cancer during treatment will also be investigated in this study.
详细描述
This is a single arm, non-interventional, uncontrolled, multicenter study in metastatic colorectal cancer patients receiving cetuximab-based infusional 5-FU regimen as 1st line treatment. Patients who are pathologically diagnosed as metastatic colorectal cancer with RAS wild type genotyping will be recruited in this study. Patients enrolled will be those for whom it is planned to treat their colorectal cancer with a cetuximab-based infusional 5-FU regimen according to the locally approved label. Cetuximab-based treatment is anticipated to be continued until disease progression, intolerable toxic effects, or withdrawal of consent occurs. Blood samples from patients enrolled in this study will be collected before the start of cetuximab-based chemotherapy, and every 3 months during the 1st line treatment with the cetuximab-based regimen. Blood sampling is also required at 2-3 weeks after disease progression following cetuximab treatment and after disease progression on 2nd line treatment. The blood samples will be sent to a central laboratory at the Taipei Institute of Pathology and evaluated for RAS genotype, using MassARRAY technique. The objectives of this study are described as follows.
Primary objective:
To observe the percentage of detected RAS mutations (circulating DNA) during 1st line cetuximab exposure in Taiwanese patients.
Secondary objective:
- To observe the time to onset of detected RAS mutation in circulating DNA.
- To observe the quantification mutation load change under treatment.
- To evaluate clinical response and resection rate of metastases with 1st line cetuximab exposure.
- To evaluate treatment duration with 1st line cetuximab.
- To investigate the correlation between the occurrence and levels of acquired RAS mutations post-cetuximab treatment and clinical outcomes (progression free survival and overall survival).
- To calculate total 1st line cetuximab exposure dosage.
- To investigate correlation between the irinotecan or oxaliplatin dosage and acquired resistance.
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
- 20 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically proven metastatic colorectal cancer for whom treatment with cetuximab in 1st line setting, is planned as part of routine clinical practice, as per the locally approved label and the best scientific information; the decision to prescribe cetuximab is at the sole discretion of the investigator. The choice of standard chemotherapy regimen for 1st line treatment of colorectal cancer is also at the sole discretion of the Investigator, based upon routine clinical practice.
- •Patients aged 20 years and above.
- •Patients who are molecularly diagnosed as having RAS wild-type mCRC.
- •Patients who are willing to provide blood samples during the study
- •Patients who are willing, and able and give, signed informed consent.
排除标准
- •Patients having a history of prior exposure to any anti-EGFR therapy.
- •Contra-indications to cetuximab as per locally approved label.
研究组 & 干预措施
RAS wild-type colorectal cancer
RAS mutation of patients who are pathologically diagnosed as metastatic colorectal cancer with RAS wild type genotyping will be evaluated using liquid biopsy during cetuximab treatment.
干预措施: Cetuximab (Drug)
RAS wild-type colorectal cancer
RAS mutation of patients who are pathologically diagnosed as metastatic colorectal cancer with RAS wild type genotyping will be evaluated using liquid biopsy during cetuximab treatment.
干预措施: liquid biopsy (Diagnostic Test)
结局指标
主要结局
Percentage of detected circulating DNA RAS mutations during 1st line cetuximab exposure.
时间窗: 9 months
Percentage of detected RAS mutations during cetuximab treatment.
次要结局
- Mutation load (percentage of detected mutated alleles) until disease progression.(9 months)
- Time to onset of newly detected circulating DNA RAS mutation.(9 months)
- Duration of treatment with cetuximab in 1st line treatment.(9 months)
- Total accumulated dosage of cetuximab in 1st line treatment.(9 months)
- Percentage of detected RAS mutations at the time of progression.(9 months)
- Clinical response rate by the investigator's judgement based on RECIST criteria.(9 months)
- Resection rate of liver or lung metastases.(9 months)
- Progression-free survival from start of 1st line treatment with cetuximab.(9 months)
- Overall survival from the start of 1st line treatment with cetuximab.(24 months)