Colorectal CancerKPLEX2NCT02784639
Comparison of KRAS/BRAF Mutational Status With Conventional Techniques and Plasma Samples Analysis
A study testing Plasma Analysis of circulating cell free DNA and Tumor tissue analysis of circulating cell free DNA in people with Colorectal Cancer, run by Institut du Cancer de Montpellier - Val d'Aurelle.
Trial summary
The goal of this multicenter prospective study is to validate, and ultimately translate in routine clinical practice, the use of plasma analysis of ccfDNA for the determination of KRAS mutation status in mCRC patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Plasma Analysis of circulating cell free DNA and Tumor tissue analysis of circulating cell free DNA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 115 participants
- Where
- No sites listed yet
- Study dates
- Oct 2013to Oct 2015
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of colorectal cancer
- Synchronous or metachronous metastatic colorectal cancer
- Patient for whom the KRAS status is requested for therapeutic decision-making
- Male or female ≥ 18 years old
- Patients must be affiliated to a Social Security System
- Patient information and written informed consent form signed prior to any study specific procedures
Who cannot join
- History of other malignancy within the previous 5 years (except for appropriately treated carcinoma in situ of the cervix and non-melanoma skin carcinoma)
- Blood transfusion within 1 week prior to blood collection
- Patients having received any chemotherapy or/and radiotherapy within 15 days prior to blood collection
- Patients with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Legal incapacity or limited legal capacity
About this study
Official title: Comparison of KRAS/BRAF Mutational Status Between Tumor Tissue Section Analysis With Conventional Techniques and Plasma Samples Analysis (KPLEX2)
The goal of this multicenter prospective study is to validate, and ultimately translate in routine clinical practice, the use of plasma analysis of ccfDNA for the determination of KRAS mutation status in mCRC patients.
Read the detailed description
Analyzing qualitatively and quantitatively genetic alterations with an efficient, simple and cost-effective test from blood samples could optimize therapeutic decision-making and personalized cancer care. Cell-free DNA (ccfDNA) levels in the plasma of CRC patients are significantly higher than in healthy patients. These levels decrease progressively in tumor-free patients during the follow-up period and increase in patients with recurrence or metastasis. In the near future, the detection of circulating DNA (ccfDNA) could therefore represent a technology breakthrough for diagnosis, prognosis, detection of tumor growth and cancer patient follow up.
We designed a refined and innovative method which simultaneously allows the determination of three parameters: the specific quantification of tumor-derived ccfDNA, the ccfDNA fragmentation index, and SNP (Single Nucleotide Polymorphism) or point mutation detection. In addition to its unprecedented sensitivity and specificity, this qPCR based-method (termed IntPlex®), recently patented by the CNRS, is easy and rapid, and the first multiplexed test for ccfDNA.
Evaluation and validation of the IntPlex® test was examined in response to the pressing need to determine the KRAS/BRAF mutational status before anti-EGFR therapy in CRC patients. As a consequence, the method was adapted to detect the six more frequent KRAS mutations in CRC (G12D, G12V, G13D, G12S, G12C, G12A) and the BRAF V600E. We then carried out the first blinded prospective study to compare KRAS and BRAF mutational status data obtained from the analysis of tumor tissue by routine gold standard methods and of plasma DNA using our original method (ASCO oral communication). The mutational status was determined by both methods in 70 patient samples. Our results clearly showed for the first time that ccfDNA analysis for KRAS mutation could replace advantageously tumor-section analysis. CcfDNA analysis showed 100% specificity and sensitivity for the BRAF V600E mutation. For the six tested KRAS point mutations, the method exhibited 100% specificity and 87% sensitivity with a concordance value of 96%.
The goal of this multicenter prospective study is to validate, and ultimately translate in routine clinical practice, the use of plasma analysis of ccfDNA for the determination of KRAS mutation status in mCRC patients.
- Conditions
- Colorectal Cancer
- Being tested
- Plasma Analysis of circulating cell free DNA, Tumor tissue analysis of circulating cell free DNA
- Keywords
- KRAS/BRAF mutational status
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma Analysis of circulating cell free DNAOther
Tumor tissue analysis of circulating cell free DNAOther
| Study group | Role | What they receive |
|---|---|---|
| determination of KRAS mutation | Other | circulating cell free DNA (ccfDNA) plasma analysis Receives: Other: Plasma Analysis of circulating cell free DNA; Other: Tumor tissue analysis of circulating cell free DNA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under ROC curve
Area under the ROC curve of the mutation percentage obtained from plasma ccfDNA analysis
Measured: 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2016 (estimated)
- Study startOct 2013
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Institut du Cancer de Montpellier - Val d'AurelleThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 115 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- MARC YCHOU, Principal investigator, Institut régional du Cancer de Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02784639
- Sponsor's protocol ID
- ICM2013/08
- Acronym
- KPLEX2
- Status last verified
- May 2016
- First submitted
- 24 May 2016
- Last updated
- 3 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of KRAS/BRAF Mutational Status Between Tumor Tissue Section Analysis With Conventional Techniques and Plasma Samples Analysis (KPLEX2)
- ClinicalTrials.gov ID
- NCT02784639
- Acronym / sponsor ID
- KPLEX2 / ICM2013/08
- Conditions
- Colorectal Cancer
- Keywords
- KRAS/BRAF mutational status
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 115 participants (actual)
- Lead sponsor
- Institut du Cancer de Montpellier - Val d'AurelleUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 27 May 2016 (estimated)
- 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.
The goal of this multicenter prospective study is to validate, and ultimately translate in routine clinical practice, the use of plasma analysis of ccfDNA for the determination of KRAS mutation status in mCRC patients.
Detailed description
Analyzing qualitatively and quantitatively genetic alterations with an efficient, simple and cost-effective test from blood samples could optimize therapeutic decision-making and personalized cancer care. Cell-free DNA (ccfDNA) levels in the plasma of CRC patients are significantly higher than in healthy patients. These levels decrease progressively in tumor-free patients during the follow-up period and increase in patients with recurrence or metastasis. In the near future, the detection of circulating DNA (ccfDNA) could therefore represent a technology breakthrough for diagnosis, prognosis, detection of tumor growth and cancer patient follow up.
We designed a refined and innovative method which simultaneously allows the determination of three parameters: the specific quantification of tumor-derived ccfDNA, the ccfDNA fragmentation index, and SNP (Single Nucleotide Polymorphism) or point mutation detection. In addition to its unprecedented sensitivity and specificity, this qPCR based-method (termed IntPlex®), recently patented by the CNRS, is easy and rapid, and the first multiplexed test for ccfDNA.
Evaluation and validation of the IntPlex® test was examined in response to the pressing need to determine the KRAS/BRAF mutational status before anti-EGFR therapy in CRC patients. As a consequence, the method was adapted to detect the six more frequent KRAS mutations in CRC (G12D, G12V, G13D, G12S, G12C, G12A) and the BRAF V600E. We then carried out the first blinded prospective study to compare KRAS and BRAF mutational status data obtained from the analysis of tumor tissue by routine gold standard methods and of plasma DNA using our original method (ASCO oral communication). The mutational status was determined by both methods in 70 patient samples. Our results clearly showed for the first time that ccfDNA analysis for KRAS mutation could replace advantageously tumor-section analysis. CcfDNA analysis showed 100% specificity and sensitivity for the BRAF V600E mutation. For the six tested KRAS point mutations, the method exhibited 100% specificity and 87% sensitivity with a concordance value of 96%.
The goal of this multicenter prospective study is to validate, and ultimately translate in routine clinical practice, the use of plasma analysis of ccfDNA for the determination of KRAS mutation status in mCRC patients.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| determination of KRAS mutation | Other | Other: Plasma Analysis of circulating cell free DNA, Other: Tumor tissue analysis of circulating cell free DNAcirculating cell free DNA (ccfDNA) plasma analysis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically confirmed diagnosis of colorectal cancer
- Synchronous or metachronous metastatic colorectal cancer
- Patient for whom the KRAS status is requested for therapeutic decision-making
- Male or female ≥ 18 years old
- Patients must be affiliated to a Social Security System
Key exclusion criteria (5 listed)
- History of other malignancy within the previous 5 years (except for appropriately treated carcinoma in situ of the cervix and non-melanoma skin carcinoma)
- Blood transfusion within 1 week prior to blood collection
- Patients having received any chemotherapy or/and radiotherapy within 15 days prior to blood collection
- Patients with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Legal incapacity or limited legal capacity
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 |
|---|---|---|
| Plasma Analysis of circulating cell free DNA | Other | determination of KRAS mutation |
| Tumor tissue analysis of circulating cell free DNA | Other | determination of KRAS mutation |
Primary outcome
Area under ROC curve
Time frame: 12 month
Area under the ROC curve of the mutation percentage obtained from plasma ccfDNA analysis
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2016.
- Individual participant dataSharing planned: No
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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.
MARC YCHOU principal investigator
Institut régional du Cancer de Montpellier
Questions about this trial
What is this clinical trial studying?
A study testing Plasma Analysis of circulating cell free DNA and Tumor tissue analysis of circulating cell free DNA in people with Colorectal Cancer, run by Institut du Cancer de Montpellier - Val d'Aurelle.
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 6 inclusion and 5 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: finished, as of the sponsor's last update on 3 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under ROC curve (time frame: 12 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Aug 2016.