NCT03401957

The Emergence of RAS Mutations in Metastatic Colorectal Cancer Patients Receiving Cetuximab Treatment

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

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 120 (estimated)
• Sponsor: National Health Research Institutes, Taiwan · Academic / Other
• Sex: All
• Age: 20 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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: 1. To observe the time to onset of detected RAS mutation in circulating DNA. 2. To observe the quantification mutation load change under treatment. 3. To evaluate clinical response and resection rate of metastases with 1st line cetuximab exposure. 4. To evaluate treatment duration with 1st line cetuximab. 5. 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). 6. To calculate total 1st line cetuximab exposure dosage. 7. To investigate correlation between the irinotecan or oxaliplatin dosage and acquired resistance.

Conditions

• Colorectal Cancer
• Drug Resistance
• Mass Spectrometry
• RAS-RAF Pathway Deregulation

Interventions

Type	Name	Description
DRUG	Cetuximab	Cetuximab-based infusional 5-FU regimen as the 1st line treatment.
DIAGNOSTIC_TEST	liquid biopsy	The blood samples taken from subjects will be evaluated for RAS genotype using MassARRAY technique.

Timeline

• Start date: 2018-01-01
• Primary completion: 2022-01-01
• Completion: 2022-01-01
• First posted: 2018-01-17
• Last updated: 2018-01-17

Locations

4 sites across 1 country: Taiwan