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

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ClinicalTrials.gov Identifier: NCT03401957
Recruitment Status : Recruiting
First Posted : January 17, 2018
Last Update Posted : January 17, 2018
Sponsor:
Collaborators:
National Cheng-Kung University Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
Taipei Veterans General Hospital, Taiwan
Cathay General Hospital
Information provided by (Responsible Party):
National Health Research Institutes, Taiwan

Brief 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.

Condition or disease Intervention/treatment
Colorectal Cancer Drug Resistance Mass Spectrometry RAS-RAF Pathway Deregulation Drug: Cetuximab Diagnostic Test: liquid biopsy

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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 120 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 18 Months
Official Title: 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
Estimated Study Start Date : January 2018
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Group/Cohort Intervention/treatment
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.
Drug: Cetuximab
Cetuximab-based infusional 5-FU regimen as the 1st line treatment.
Other Name: erbitux

Diagnostic Test: liquid biopsy
The blood samples taken from subjects will be evaluated for RAS genotype using MassARRAY technique.




Primary Outcome Measures :
  1. Percentage of detected circulating DNA RAS mutations during 1st line cetuximab exposure. [ Time Frame: 9 months ]
    Percentage of detected RAS mutations during cetuximab treatment.


Secondary Outcome Measures :
  1. Time to onset of newly detected circulating DNA RAS mutation. [ Time Frame: 9 months ]
    Time duration between the start of cetuximab treatment and newly detection of RAS mutation.

  2. Mutation load (percentage of detected mutated alleles) until disease progression. [ Time Frame: 9 months ]
    Percentage of detected mutated alleles at disease progression.

  3. Percentage of detected RAS mutations at the time of progression. [ Time Frame: 9 months ]
    Percentage of detected RAS mutations at the time of progression.

  4. Clinical response rate by the investigator's judgement based on RECIST criteria. [ Time Frame: 9 months ]
    Response rate of tumor after cetuximab treatment.

  5. Resection rate of liver or lung metastases. [ Time Frame: 9 months ]
    Resection rates of metastases after cetuximab treatment.

  6. Duration of treatment with cetuximab in 1st line treatment. [ Time Frame: 9 months ]
    Time duration of cetuximab as the 1st line treatment.

  7. Total accumulated dosage of cetuximab in 1st line treatment. [ Time Frame: 9 months ]
    Total accumulated dosage of cetuximab in 1st line treatment.

  8. Progression-free survival from start of 1st line treatment with cetuximab. [ Time Frame: 9 months ]
    The time duration of subjects between the inclusion in the study and disease progression.

  9. Overall survival from the start of 1st line treatment with cetuximab. [ Time Frame: 24 months ]
    The time duration of subjects between the inclusion in the study and death.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with RAS wild-type metastatic colorectal cancer receiving cetuximab-based regimen (5-FU containing) as the 1st line treatment.
Criteria

Inclusion Criteria:

  1. 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.
  2. Patients aged 20 years and above.
  3. Patients who are molecularly diagnosed as having RAS wild-type mCRC.
  4. Patients who are willing to provide blood samples during the study
  5. Patients who are willing, and able and give, signed informed consent.

Exclusion Criteria:

  1. Patients having a history of prior exposure to any anti-EGFR therapy.
  2. Contra-indications to cetuximab as per locally approved label.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03401957


Contacts
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Contact: Shang Hung Chen, M.D. +886-6-7000123 ext 65113 bryanchen@nhri.org.tw

Locations
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Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital Recruiting
Kaohsiung, Taiwan
Contact: Jaw-Yuan Wang, M.D.       jayuwa@cc.kmu.edu.tw   
National Cheng Kung University Hospital Recruiting
Tainan, Taiwan
Contact: Shang Hung Chen, M.D.    +886-6-7000123 ext 65113    bryanchen@nhri.org.tw   
Cathay General Hospital Not yet recruiting
Taipei, Taiwan
Contact: Yung-Chuan Sung, M.D.       yungchuans@cgh.org.tw   
Taipei Veterans General Hospital Recruiting
Taipei, Taiwan
Contact: Jeng-Kai Jiang, M.D.       jkjiang@vghtpe.gov.tw   
Sponsors and Collaborators
National Health Research Institutes, Taiwan
National Cheng-Kung University Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
Taipei Veterans General Hospital, Taiwan
Cathay General Hospital
Investigators
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Principal Investigator: Li-Tzong Chen, M.D. National Institute of Cancer Research, National Health Research Institutes
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Health Research Institutes, Taiwan
ClinicalTrials.gov Identifier: NCT03401957    
Other Study ID Numbers: EC1060904
First Posted: January 17, 2018    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Health Research Institutes, Taiwan:
colorectal cancer
cetuximab resistance
liquid biopsy
RAS mutation
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents