Metastatic Colorectal CancerNCT01996969
Identification of Predictive Biomarker of Regorafenib in Refractory Colorectal Cancer
A study testing Regorafenib in people with Metastatic Colorectal Cancer, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
Regorafenib is a valuable treatment option for metastatic colorectal cancer patients who have progressed after prior standard treatments. Prior progression-free survival data suggest that there could be a distinct subgroup of patients that may benefit from regorafenib. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Regorafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 1 siteSouth Korea
- Study dates
- Oct 2013to May 2016
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent obtained before any study-specific procedures.
- Age ≥ 20
- Pathologically confirmed metastatic adenocarcinoma of colon or rectum
- Failure of standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan. Failure is defined as progression during or within 3 months following the last administration of therapy. Patients who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent before progression of disease will also be allowed into the study. Patients treated with oxaliplatin in an adjuvant setting who have progressed during or within 6 months of completion of adjuvant therapy are regarded as failure of oxaliplatin. Patients may or may not have received bevacizumab or cetuximab.
- Measurable or nonmeasurable disease according to RECIST criteria, version 1.1.
- Adequate tissue for gene sequencing (surgical FFPE specimen or fresh-frozen biopsy specimen)
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- ECOG PS 0 or 1
- Life expectancy of at least 3 months
- Adequate bone-marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 14 days of starting to study treatment
- Total bilirubin ≤1.5 × ULN
- Alanine aminotransferase and aspartate aminotransferase ≤2 × ULN (≤5 × ULN for patients with liver involvement of cancer)
- Amylase and lipase ≤1.5 × ULN
- Serum creatinine ≤1.5 × ULN
- Glomerular filtration rate ≥30 ml/min/1.73 m2 according to the Modified Diet in Renal Disease abbreviated formula
- International normalised ratio (INR) and partial thromboplastin time (PTT) ≤1.5 × ULN. Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of an underlying abnormality in coagulation parameters exists.
- Platelet count ≥100,000/mm3, haemoglobin >9 g/dl, absolute neutrophil count >1,500/mm3
- Alkaline phosphatase limit ≤2.5 × ULN (≤5 × ULN for patients with liver involvement of their cancer)
Who cannot join
- Prior treatment with regorafenib
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
- Pregnancy or breast-feeding. Women of childbearing potential must have a negative pregnancy test performed a maximum of 7 days before start of treatment
- Congestive heart failure of NYHA class 2 or worse
- Unstable angina, new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study drug
- Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
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- Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic >90 mmHg despite optimal medical management)
- Arterial or venous thrombotic or embolic events within the 6 months before start of study medication
- Ongoing infection higher than NCI-CTCAE v4.0 grade 2
- Known history of HIV infection
- Active hepatitis B or C virus infection
- Seizure disorder requiring medication
- Symptomatic metastatic brain or meningeal tumors
- History of organ allograft
- Non-healing wound, ulcer, or bone fracture
- Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
- Persistent proteinuria of NCI-CTCAE v4.0 grade 3 or higher
- Inability to swallow oral medications
- Any malabsorption condition
- Unresolved toxicity higher than NCI-CTCAE v4.0 grade 1 attributed to any prior therapy/procedure, excluding alopecia and oxaliplatin-induced neurotoxicity of grade 2 or less
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Identification of Predictive Biomarker of Regorafenib in Refractory Colorectal Cancer: A Prospective Explorative Study
Regorafenib is a valuable treatment option for metastatic colorectal cancer patients who have progressed after prior standard treatments. Prior progression-free survival data suggest that there could be a distinct subgroup of patients that may benefit from regorafenib. The aim of this study is to identify predictive biomarker of regorafenib in terms of its efficacy.
Read the detailed description
Regorafenib is a multi-tyrosine kinase inhibitor which has been shown to increase survival in metastatic colorectal cancer patients who have progressed after prior standard treatments. Progression-free survival data suggest that there could be a distinct subgroup of patients that may benefit from regorafenib. Therefore, it would be important to identify predictive biomarker of efficacy of regorafenib. Considering that regorafenib is a multi-tyrosine kinase inhibitor, comprehensive approach is required to discover predictive biomarker.
NGS-based sequencing allows generating large amount of data regarding multiple genes and multiple genetic alterations within a single experiment. Also, it requires less amount of DNA or tissue and cost compared to currently used individual gene testing techniques such as direct sequencing or FISH. Moreover, superior sensitivity over Sanger sequencing can be obtained by increasing coverage depth, especially in cases with low tumor purity. Wide range of genes targeted by regorafenib and genes in the major oncogenic pathway of colorectal cancer influenced by regorafenib can be efficiently assessed using NGS-based sequencing.
The aim of this study is to identify predictive biomarker of efficacy of regorafeinib in metastatic, refractory colorectal cancer patients using NGS technology.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Regorafenib
- Keywords
- metastatic colorectal cancer, refractory, regorafenib, biomarker, gene sequencing
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RegorafenibDrug
Regorafenib will be given 160mg once daily for 3 weeks, followed by a 1 week rest. Treatment will be continued until disease progression or unacceptable toxicity occurs. Response evaluation (CT scans) will be performed every 2 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib | Other | This study is a single arm study with biomarker analysis Receives: Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Predictive biomarker in terms of disease control rate
This study aims at identifying potential molecular subgroup of colorectal cancer that may benefit from regorafenib treatment in terms of disease control rate.
Measured: 1 year
Secondary outcomes (7)
Disease control rate
Disease control rate in all treated population
Measured: 1 year
Progression-free survival
Progression-free survival in all treated population
Measured: 1 year
Overall survival
Overall survival in all treated population
Measured: 1 year
number of participants with adverse events
adverse events according to NCI-CTCAE v.4.0
Measured: 1 year
Progression-free survival according to biomarker status
Progression-free survivals will be compared according to biomarker status
Measured: 1 year
Overall survival according to biomarker status
Overall survivals will be compared according to biomarker status
Measured: 1 year
Assessment of adequate response evaluation modality after regorafenib treatment
Changes in size, CT attenuation (HFU) and PET metabolism (SUV) will be evaluated and assessed in relation to survival outcomes
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2013 (estimated)
- Study startOct 2013
- Primary completionJun 2015
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe 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
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Tae-You Kim, Seoul National University Hospital
- Investigators
- Tae-You Kim, M.D., Ph.D, Principal investigator, Seoul National University HospitalSae-Won Han, M.D.,Ph.D, Study director, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01996969
- Sponsor's protocol ID
- Regorafenib biomarker
- Status last verified
- Feb 2019
- First submitted
- 24 Oct 2013
- Last updated
- 22 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Predictive Biomarker of Regorafenib in Refractory Colorectal Cancer: A Prospective Explorative Study
- ClinicalTrials.gov ID
- NCT01996969
- Acronym / sponsor ID
- Regorafenib biomarker
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- metastatic colorectal cancer, refractory, regorafenib, biomarker, gene sequencing
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Oct 2013
- Primary completion
- Jun 2015 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 27 Nov 2013 (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.
Regorafenib is a valuable treatment option for metastatic colorectal cancer patients who have progressed after prior standard treatments. Prior progression-free survival data suggest that there could be a distinct subgroup of patients that may benefit from regorafenib. The aim of this study is to identify predictive biomarker of regorafenib in terms of its efficacy.
Detailed description
Regorafenib is a multi-tyrosine kinase inhibitor which has been shown to increase survival in metastatic colorectal cancer patients who have progressed after prior standard treatments. Progression-free survival data suggest that there could be a distinct subgroup of patients that may benefit from regorafenib. Therefore, it would be important to identify predictive biomarker of efficacy of regorafenib. Considering that regorafenib is a multi-tyrosine kinase inhibitor, comprehensive approach is required to discover predictive biomarker.
NGS-based sequencing allows generating large amount of data regarding multiple genes and multiple genetic alterations within a single experiment. Also, it requires less amount of DNA or tissue and cost compared to currently used individual gene testing techniques such as direct sequencing or FISH. Moreover, superior sensitivity over Sanger sequencing can be obtained by increasing coverage depth, especially in cases with low tumor purity. Wide range of genes targeted by regorafenib and genes in the major oncogenic pathway of colorectal cancer influenced by regorafenib can be efficiently assessed using NGS-based sequencing.
The aim of this study is to identify predictive biomarker of efficacy of regorafeinib in metastatic, refractory colorectal cancer patients using NGS technology.
Study design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib | Other | Drug: RegorafenibThis study is a single arm study with biomarker analysis |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Signed informed consent obtained before any study-specific procedures.
- Age ≥ 20
- Pathologically confirmed metastatic adenocarcinoma of colon or rectum
- Failure of standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan. Failure is defined as progression during or within 3 months following the last administration of therapy. Patients who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent before progression of disease will also be allowed into the study. Patients treated with oxaliplatin in an adjuvant setting who have progressed during or within 6 months of completion of adjuvant therapy are regarded as failure of oxaliplatin. Patients may or may not have received bevacizumab or cetuximab.
- Measurable or nonmeasurable disease according to RECIST criteria, version 1.1.
Key exclusion criteria (20 listed)
- Prior treatment with regorafenib
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
- Pregnancy or breast-feeding. Women of childbearing potential must have a negative pregnancy test performed a maximum of 7 days before start of treatment
- Congestive heart failure of NYHA class 2 or worse
- Unstable angina, new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study drug
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 |
|---|---|---|
| RegorafenibRegorafenib will be given 160mg once daily for 3 weeks, followed by a 1 week rest. Treatment will be continued until disease progression or unacceptable toxicity occurs. Response evaluation (CT scans) will be performed every 2 cycles. | Drug | Regorafenib |
Primary outcome
Predictive biomarker in terms of disease control rate
Time frame: 1 year
This study aims at identifying potential molecular subgroup of colorectal cancer that may benefit from regorafenib treatment in terms of disease control rate.
7 secondary outcomes
Disease control rate
Time frame: 1 year
Progression-free survival
Time frame: 1 year
Overall survival
Time frame: 1 year
number of participants with adverse events
Time frame: 1 year
Progression-free survival according to biomarker status
Time frame: 1 year
Overall survival according to biomarker status
Time frame: 1 year
Assessment of adequate response evaluation modality after regorafenib treatment
Time frame: 1 year
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 22 Feb 2019.
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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.
Tae-You Kim, M.D., Ph.D principal investigator
Seoul National University Hospital
Sae-Won Han, M.D.,Ph.D study director
Seoul National University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Regorafenib in people with Metastatic Colorectal Cancer, run by Seoul National University Hospital at 1 site in South Korea.
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 17 inclusion and 20 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 22 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. 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?
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?
Predictive biomarker in terms of disease control rate (time frame: 1 year). 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 22 Feb 2019.