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

NCT ID: NCT03401957

Last Updated: 2018-01-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

120 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-01-31

Study Completion Date

2022-01-31

Brief Summary

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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

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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

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Colorectal Cancer Drug Resistance Mass Spectrometry RAS-RAF Pathway Deregulation

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Cetuximab

Intervention Type DRUG

Cetuximab-based infusional 5-FU regimen as the 1st line treatment.

liquid biopsy

Intervention Type DIAGNOSTIC_TEST

The blood samples taken from subjects will be evaluated for RAS genotype using MassARRAY technique.

Interventions

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Cetuximab

Cetuximab-based infusional 5-FU regimen as the 1st line treatment.

Intervention Type DRUG

liquid biopsy

The blood samples taken from subjects will be evaluated for RAS genotype using MassARRAY technique.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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erbitux

Eligibility Criteria

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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.
Minimum Eligible Age

20 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cheng-Kung University Hospital

OTHER

Sponsor Role collaborator

Kaohsiung Medical University Chung-Ho Memorial Hospital

OTHER

Sponsor Role collaborator

Taipei Veterans General Hospital, Taiwan

OTHER_GOV

Sponsor Role collaborator

Cathay General Hospital

OTHER

Sponsor Role collaborator

National Health Research Institutes, Taiwan

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Li-Tzong Chen, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Cancer Research, National Health Research Institutes

Locations

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Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status RECRUITING

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status RECRUITING

Cathay General Hospital

Taipei, , Taiwan

Site Status NOT_YET_RECRUITING

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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Shang Hung Chen, M.D.

Role: CONTACT

+886-6-7000123 ext. 65113

Facility Contacts

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Jaw-Yuan Wang, M.D.

Role: primary

Shang Hung Chen, M.D.

Role: primary

+886-6-7000123 ext. 65113

Yung-Chuan Sung, M.D.

Role: primary

Jeng-Kai Jiang, M.D.

Role: primary

References

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Tsai HL, Lin CC, Sung YC, Chen SH, Chen LT, Jiang JK, Wang JY. The emergence of RAS mutations in patients with RAS wild-type mCRC receiving cetuximab as first-line treatment: a noninterventional, uncontrolled multicenter study. Br J Cancer. 2023 Oct;129(6):947-955. doi: 10.1038/s41416-023-02366-z. Epub 2023 Jul 24.

Reference Type DERIVED
PMID: 37488448 (View on PubMed)

Chen SH, Tsai HL, Jiang JK, Sung YC, Huang CW, Yeh YM, Chen LT, Wang JY. Emergence of RAS mutations in patients with metastatic colorectal cancer receiving cetuximab-based treatment: a study protocol. BMC Cancer. 2019 Jun 28;19(1):640. doi: 10.1186/s12885-019-5826-7.

Reference Type DERIVED
PMID: 31253124 (View on PubMed)

Other Identifiers

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EC1060904

Identifier Type: -

Identifier Source: org_study_id

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