Colorectal CancerNCT03401957
The Emergence of RAS Mutations in Metastatic Colorectal Cancer Patients Receiving Cetuximab Treatment
An observational study of Colorectal Cancer and Drug Resistance, run by National Health Research Institutes, Taiwan at 4 sites in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 90 years
- Conditions the study is for
- Colorectal Cancer, Drug Resistance, Mass Spectrometry
- What is being tested?
- Cetuximab and liquid biopsy
- How many people
- 120 participants
- Where
- 4 sitesTaiwan
- Study dates
- Jan 2018to Jan 2022
- How long will I take part?
- 18 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with RAS wild-type metastatic colorectal cancer receiving cetuximab-based regimen (5-FU containing) as the 1st line treatment.
Who may be able to join
- 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.
Who cannot join
- Patients having a history of prior exposure to any anti-EGFR therapy.
- Contra-indications to cetuximab as per locally approved label.
Trial locations and contacts
4 sites in 1 country.
Taiwan4 sites, 4 recruiting
- Recruiting
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City
Jaw-Yuan Wang, M.D., jayuwa@cc.kmu.edu.tw
- Recruiting
National Cheng Kung University Hospital
Tainan
Shang Hung Chen, M.D., +886-6-7000123 ext. 65113, bryanchen@nhri.org.tw
- Not yet recruiting
Cathay General Hospital
Taipei
Yung-Chuan Sung, M.D., yungchuans@cgh.org.tw
- Recruiting
Taipei Veterans General Hospital
Taipei
Jeng-Kai Jiang, M.D., jkjiang@vghtpe.gov.tw
About this study
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
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.
Read the 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:
- 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.
- Being tested
- Cetuximab, liquid biopsy
- Keywords
- colorectal cancer, cetuximab resistance, liquid biopsy, RAS mutation
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Also called erbitux
Cetuximab-based infusional 5-FU regimen as the 1st line treatment.
liquid biopsyDiagnostic test
The blood samples taken from subjects will be evaluated for RAS genotype using MassARRAY technique.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Cetuximab; Diagnostic Test: liquid biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of detected circulating DNA RAS mutations during 1st line cetuximab exposure.
Percentage of detected RAS mutations during cetuximab treatment.
Measured: 9 months
Secondary outcomes (9)
Time to onset of newly detected circulating DNA RAS mutation.
Time duration between the start of cetuximab treatment and newly detection of RAS mutation.
Measured: 9 months
Mutation load (percentage of detected mutated alleles) until disease progression.
Percentage of detected mutated alleles at disease progression.
Measured: 9 months
Percentage of detected RAS mutations at the time of progression.
Percentage of detected RAS mutations at the time of progression.
Measured: 9 months
Clinical response rate by the investigator's judgement based on RECIST criteria.
Response rate of tumor after cetuximab treatment.
Measured: 9 months
Resection rate of liver or lung metastases.
Resection rates of metastases after cetuximab treatment.
Measured: 9 months
Duration of treatment with cetuximab in 1st line treatment.
Time duration of cetuximab as the 1st line treatment.
Measured: 9 months
Total accumulated dosage of cetuximab in 1st line treatment.
Total accumulated dosage of cetuximab in 1st line treatment.
Measured: 9 months
Progression-free survival from start of 1st line treatment with cetuximab.
The time duration of subjects between the inclusion in the study and disease progression.
Measured: 9 months
Overall survival from the start of 1st line treatment with cetuximab.
The time duration of subjects between the inclusion in the study and death.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2018
- Study startJan 2018 (estimated)
- Primary completionJan 2022 (estimated)
- Study completionJan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 120 participants (estimated)
- Target duration
- 18 Months
Sponsor and investigators
- Lead sponsor
- National Health Research Institutes, Taiwan
- Sponsor type
- University, hospital or other
- Collaborators
- National Cheng-Kung University Hospital, Kaohsiung Medical University Chung-Ho Memorial Hospital, Taipei Veterans General Hospital, Taiwan, Cathay General Hospital
- Responsible party
- Sponsor
- Investigators
- Li-Tzong Chen, M.D., Principal investigator, National Institute of Cancer Research, National Health Research Institutes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03401957
- Sponsor's protocol ID
- EC1060904
- Status last verified
- Jan 2018
- First submitted
- 10 Jan 2018
- Last updated
- 17 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 37488448Chen 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.
PubMed 31253124
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03401957
- Acronym / sponsor ID
- EC1060904
- Keywords
- colorectal cancer, cetuximab resistance, liquid biopsy, RAS mutation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- National Health Research Institutes, TaiwanUniversity, hospital or other
- Collaborators
- National Cheng-Kung University Hospital, Kaohsiung Medical University Chung-Ho Memorial Hospital, Taipei Veterans General Hospital, Taiwan, Cathay General Hospital
- Study start
- Jan 2018 (estimated)
- Primary completion
- Jan 2022 (estimated)
- Study completion
- Jan 2022 (estimated)
- First posted
- 17 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 18 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAS wild-type colorectal cancer | – | Drug: Cetuximab, Diagnostic Test: liquid biopsyRAS 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. |
Who may qualify
- Ages
- 20 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with RAS wild-type metastatic colorectal cancer receiving cetuximab-based regimen (5-FU containing) as the 1st line treatment.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (2 listed)
- Patients having a history of prior exposure to any anti-EGFR therapy.
- Contra-indications to cetuximab as per locally approved label.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CetuximabAlso: erbituxCetuximab-based infusional 5-FU regimen as the 1st line treatment. | Drug | RAS wild-type colorectal cancer |
| liquid biopsyThe blood samples taken from subjects will be evaluated for RAS genotype using MassARRAY technique. | Diagnostic test | RAS wild-type colorectal cancer |
Primary outcome
Percentage of detected circulating DNA RAS mutations during 1st line cetuximab exposure.
Time frame: 9 months
Percentage of detected RAS mutations during cetuximab treatment.
9 secondary outcomes
Time to onset of newly detected circulating DNA RAS mutation.
Time frame: 9 months
Mutation load (percentage of detected mutated alleles) until disease progression.
Time frame: 9 months
Percentage of detected RAS mutations at the time of progression.
Time frame: 9 months
Clinical response rate by the investigator's judgement based on RECIST criteria.
Time frame: 9 months
Resection rate of liver or lung metastases.
Time frame: 9 months
Duration of treatment with cetuximab in 1st line treatment.
Time frame: 9 months
Total accumulated dosage of cetuximab in 1st line treatment.
Time frame: 9 months
Progression-free survival from start of 1st line treatment with cetuximab.
Time frame: 9 months
Overall survival from the start of 1st line treatment with cetuximab.
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2018.
- Derived from this study: PubMed 37488448Tsai 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.
- Derived from this study: PubMed 31253124Chen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Li-Tzong Chen, M.D. principal investigator
National Institute of Cancer Research, National Health Research Institutes
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colorectal Cancer and Drug Resistance, run by National Health Research Institutes, Taiwan at 4 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shang Hung Chen, M.D. (+886-6-7000123 ext. 65113, bryanchen@nhri.org.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of detected circulating DNA RAS mutations during 1st line cetuximab exposure. (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03401957, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2018.