Metastatic Colorectal CancerPhase 2NCT03880877
Regorafenib Plus FOLFIRI With Irinotecan Dose Escalated in Patients With Previously Treated Metastatic Colorectal Cancer
A Phase 2 study testing Regorafenib, UGT1A1 genotyping (TA6/TA6) and UGT1A1 genotyping (TA6/TA7) in people with Metastatic Colorectal Cancer, run by Kaohsiung Medical University Chung-Ho Memorial Hospital at 1 site in Taiwan.
Trial summary
A prospective, multicenter, randomized in a 2:1 ratio, controlled, clinical trial with two parallel arms will be conducted to compare irinotecan dose escalated FOLFIRI according to UGT1A1 genotyping plus 120 mg regorafenib with 120 mg regorafenib alone in previously treated patients with metastatic colorectal cancer… Read more about this study
- Who is it for?
- Ages 20 to 85 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Regorafenib, UGT1A1 genotyping (TA6/TA6) and UGT1A1 genotyping (TA6/TA7)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 153 participants
- Where
- 1 siteTaiwan
- Study dates
- 26 Feb 2019to 31 Dec 2021
- Phase
- Phase 2
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cyto-/histological confirmed mCRC
- Patients who have been previously treated with, or are not considered candidates for, other locally approved standard treatment(s) and for whom the decision has been made per investigator's routine treatment practice to prescribe regorafenib as 3rd line (RAS mutant) or 4th line (RAS wild type) therapy
- Aged no less than 20 years, at the time of acquisition of informed consent
- Eastern Cooperative Oncology Group (ECOG) performance score of 0-1
- Patients with measurable or non-measurable disease in the colon or rectum, according to RECIST criteria version 1.1
- Life expectancy more than 12 weeks
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- Women with childbearing potential must agree to perform adequate contraception measures since informed consent till a least 12 weeks after the last study drug administration.
- The investigators or designee are requested to advise the patient to achieve adequate birth control.
- Adequate organ and bone marrow function as defined below:
- Total bilirubin <= 1.5 x the upper limit of normal (ULN)
- Alanine amino-transferase (ALT) and aspartate amino-transferase (AST) <= 2.5 x ULN (<= 5 x ULN for patients with liver metastases)
- Alkaline phosphatase (ALP) <= 2.5 x ULN (<= 5 x ULN for patients with liver metastases)
- Amylase and lipase <= 1.5 x ULN
- Serum creatinine <= 1.5 x ULN
- Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m2, according to the modified diet in renal disease (MDRD) abbreviated formula
- International normalized ratio (INR)/partial thromboplastin time (PTT) <= 1.5 x ULN
- Platelet counts >= 100,000/mm3
- Hemoglobin level >= 9 g/dL
- Absolute neutrophil counts >= 1,500/mm3
- Ability to understand and willingness to sign written Informed Consent Form (ICF)
Who cannot join
- Prior treatment with regorafenib within 28 days
- Other concurrent cancer or prior treatment for other carcinomas within the last five years, except curatively treated non-melanoma skin cancer, superficial bladder tumors, and cervical cancer in-situ
- Extended field radiotherapy within 28 days or limited radiotherapy within 14 days prior to randomization
- Major surgery within 28 days prior to start of study treatment (diagnostic biopsy, laparotomy, line placement is not considered as major surgery)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction in the past 12 months, active gastrointestinal bleeding, central nervous system disorders or psychiatric illness/social situation that would limit compliance with study requirements or judged to be ineligible for the study by the investigator
- History of myocardial infarction, deep venous or arterial thrombosis, or cardiovascular accident (CVA) during the last 6 months
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- Uncontrolled cardiac arrhythmias, unstable angina, or newly-onset angina within 3 months prior to study entry
- Uncontrolled hypertension despite optimal management (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg)
- Patients with known central nervous system (CNS) metastases
- Having received any investigational agents or participating in any investigational drug study within 4 weeks prior to study enrollment
- Pregnant or breast-feeding female (a pregnancy test must be performed on all female patients with child-bearing potential within 7 days of treatment initiation, and the result must be negative)
- Inability to take oral medications
- Poor compliance as judged by the investigator
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Chung-Ho Memorial Hospital, Kaohsiung Medical University:
Kaohsiung City, 807
Jaw-Yuan Wang, PhD, chunpin870132@yahoo.com.tw
Jaw-Yuan Wang, Ph.D.
About this study
Official title: Regorafenib Plus FOLFIRI With Irinotecan Dose Escalated According to UGT1A1 Genotyping Versus Regorafenib Monotherapy in Patients With Previously Treated Metastatic Colorectal Cancer: A Prospective, Randomized, Controlled Study
A prospective, multicenter, randomized in a 2:1 ratio, controlled, clinical trial with two parallel arms will be conducted to compare irinotecan dose escalated FOLFIRI according to UGT1A1 genotyping plus 120 mg regorafenib with 120 mg regorafenib alone in previously treated patients with metastatic colorectal cancer (mCRC).
Read the detailed description
Primary objective:
Progression-free survival
Secondary objective:
Overall survival, best objective response, disease control rate, time to progression, duration of treatment and adverse events
Number of Subjects: 153 patients with metastatic colorectal cancer treated with regorafenib and FOLFIRI as a third- or fourth-line setting.
Plan of the Study:
- This is a prospective, multicenter, randomized in a 2:1 ratio, controlled study.
- Study Schedule Study date: the time getting approval letter issued by both regulatory authority and institutional review board (IRB). Duration of the study: 4 years.
- Duration of Treatment: Treatment was administered until disease progressed.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Regorafenib, UGT1A1 genotyping (TA6/TA6), UGT1A1 genotyping (TA6/TA7), UGT1A1 genotyping (TA7/TA7), Leucovorin and 5-FU
- Keywords
- metastatic colorectal cancer, FOLFIRI, regorafenib
- 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
Also called stivarga
Regorafenib is administered at dose of 120 mg daily for 3 weeks in a 4-week cycle
UGT1A1 genotyping (TA6/TA6)Genetic
The dosage of irinotecan in FOLFIRI is escalated from 180mg/m2 to 260 mg/m2
UGT1A1 genotyping (TA6/TA7)Genetic
The dosage of irinotecan in FOLFIRI is escalated from 180mg/m2 to 240 mg/m2
UGT1A1 genotyping (TA7/TA7)Genetic
The dosage of irinotecan in FOLFIRI is escalated from 120mg/m2 to180 mg/m2
Leucovorin and 5-FUDrug
Leucovorin (400 mg/m2 IV infusion over 2 hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period)
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib plus FOLFIRI | Experimental | Regimen for treatment consists of irinotecan (180 mg/m2 as a 120-min IV infusion for UGT1A1 genotyping (TA6/TA6) and UGT1A1 genotyping (TA6/TA7); 120 mg/m2 as a 120-min IV infusion for UGT1A1 genotyping (TA7/TA7)), followed by Leucovorin (400 mg/m2 IV infusion over 2 hours), and fluorouracil (5-FU) (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.
After every 2 cycles of each different dose of irinotecan, if adverse events (AEs) are under the grade 2, we will escalate the dose of 30 mg/m2. The estimated maximal dose of irinotecan is 260 mg/m2 for UGT1A1 genotyping (TA6/TA6); 240 mg/m2 for UGT1A1 genotyping (TA6/TA7); 180 mg/m2 for UGT1A1 genotyping (TA7/TA7).
Regorafenib is administered at adjusted dosage of 120 mg daily for 3 weeks in a 4-week cycle. Receives: Drug: Regorafenib; Genetic: UGT1A1 genotyping (TA6/TA6); Genetic: UGT1A1 genotyping (TA6/TA7); Genetic: UGT1A1 genotyping (TA7/TA7); Drug: Leucovorin and 5-FU |
| Regorafenib | Active comparator | Regorafenib is administered at adjusted dosage of 120 mg daily for 3 weeks in a 4-week cycle. Receives: Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
Time from treatment to disease progresses and lives
Measured: From date of initiation of treatment until the date of first documented progression, assessed up to 23 months
Secondary outcomes (5)
Overall survival
Time from treatment to death of patients
Measured: From date of initiation of treatment until the date of death from any cause, assessed up to 23 months
Best objective response
best response recorded during treatment
Measured: From date of initiation of treatment until the date of disease progression, assessed up to 23 months
Disease control rate
Rate of best objective response, including complete response, partial response and stable disease
Measured: From date of initiation of treatment until the date of disease progression, assessed up to 23 months
Time to progression
Time from treatment to disease progresses
Measured: From date of initiation of treatment until the date of disease progression, assessed up to 23 months
Duration of treatment
Time from initiation to termination of treatment
Measured: From date of initiation of treatment until the date of disease progression, assessed up to 23 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2019
- Study start26 Feb 2019
- Primary completion1 Mar 2021 (estimated)
- Study completion31 Dec 2021 (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 Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Kaohsiung Medical University Chung-Ho Memorial 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 153 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jaw-Yuan Wang, MD, PhD, Kaohsiung Medical University Chung-Ho Memorial Hospital
- Investigators
- Jaw-Yuan Wang, PhD, Study chair, Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03880877
- Sponsor's protocol ID
- KMUHIRB-F(II)-20190032
- Status last verified
- Mar 2019
- First submitted
- 17 Mar 2019
- Last updated
- 21 Mar 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Huang CW, Chen YC, Ker TW, Lin YW, Chang TK, Su WC, Chen PJ, Tsai HL, Wang JY. Efficacy and safety of regorafenib plus FOLFIRI with UGT1A1 genotyping-guided irinotecan dose escalation against metastatic colorectal cancer: a multicenter, phase II, open-label, two-arm randomized controlled tria. Ther Adv Med Oncol. 2025 Oct 23;17:17588359251371489. doi: 10.1177/17588359251371489. eCollection 2025.
PubMed 41164204Ma CJ, Chang TK, Tsai HL, Su WC, Huang CW, Yeh YS, Chang YT, Wang JY. Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trial. Trials. 2019 Dec 19;20(1):751. doi: 10.1186/s13063-019-3917-z.
PubMed 31856912
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regorafenib Plus FOLFIRI With Irinotecan Dose Escalated According to UGT1A1 Genotyping Versus Regorafenib Monotherapy in Patients With Previously Treated Metastatic Colorectal Cancer: A Prospective, Randomized, Controlled Study
- ClinicalTrials.gov ID
- NCT03880877
- Acronym / sponsor ID
- KMUHIRB-F(II)-20190032
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- metastatic colorectal cancer, FOLFIRI, regorafenib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 153 participants (estimated)
- Lead sponsor
- Kaohsiung Medical University Chung-Ho Memorial HospitalUniversity, hospital or other
- Study start
- 26 Feb 2019 (actual)
- Primary completion
- 1 Mar 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 19 Mar 2019 (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.
A prospective, multicenter, randomized in a 2:1 ratio, controlled, clinical trial with two parallel arms will be conducted to compare irinotecan dose escalated FOLFIRI according to UGT1A1 genotyping plus 120 mg regorafenib with 120 mg regorafenib alone in previously treated patients with metastatic colorectal cancer (mCRC).
Detailed description
Primary objective:
Progression-free survival
Secondary objective:
Overall survival, best objective response, disease control rate, time to progression, duration of treatment and adverse events
Number of Subjects: 153 patients with metastatic colorectal cancer treated with regorafenib and FOLFIRI as a third- or fourth-line setting.
Plan of the Study:
- This is a prospective, multicenter, randomized in a 2:1 ratio, controlled study.
- Study Schedule Study date: the time getting approval letter issued by both regulatory authority and institutional review board (IRB). Duration of the study: 4 years.
- Duration of Treatment: Treatment was administered until disease progressed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Regorafenib plus FOLFIRI | Experimental | Drug: Regorafenib, Genetic: UGT1A1 genotyping (TA6/TA6), Genetic: UGT1A1 genotyping (TA6/TA7), Genetic: UGT1A1 genotyping (TA7/TA7), Drug: Leucovorin and 5-FURegimen for treatment consists of irinotecan (180 mg/m2 as a 120-min IV infusion for UGT1A1 genotyping (TA6/TA6) and UGT1A1 genotyping (TA6/TA7); 120 mg/m2 as a 120-min IV infusion for UGT1A1 genotyping (TA7/TA7)), followed by Leucovorin (400 mg/m2 IV infusion over 2 hours), and fluorouracil (5-FU) (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks. After every 2 cycles of each different dose of irinotecan, if adverse events (AEs) are under the grade 2, we will escalate the dose of 30 mg/m2. The estimated maximal dose of irinotecan is 260 mg/m2 for UGT1A1 genotyping (TA6/TA6); 240 mg/m2 for UGT1A1 genotyping (TA6/TA7); 180 mg/m2 for UGT1A1 genotyping (TA7/TA7). Regorafenib is administered at adjusted dosage of 120 mg daily for 3 weeks in a 4-week cycle. |
| Regorafenib | Active comparator | Drug: RegorafenibRegorafenib is administered at adjusted dosage of 120 mg daily for 3 weeks in a 4-week cycle. |
Who may qualify
- Ages
- 20 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Cyto-/histological confirmed mCRC
- Patients who have been previously treated with, or are not considered candidates for, other locally approved standard treatment(s) and for whom the decision has been made per investigator's routine treatment practice to prescribe regorafenib as 3rd line (RAS mutant) or 4th line (RAS wild type) therapy
- Aged no less than 20 years, at the time of acquisition of informed consent
- Eastern Cooperative Oncology Group (ECOG) performance score of 0-1
- Patients with measurable or non-measurable disease in the colon or rectum, according to RECIST criteria version 1.1
Key exclusion criteria (13 listed)
- Prior treatment with regorafenib within 28 days
- Other concurrent cancer or prior treatment for other carcinomas within the last five years, except curatively treated non-melanoma skin cancer, superficial bladder tumors, and cervical cancer in-situ
- Extended field radiotherapy within 28 days or limited radiotherapy within 14 days prior to randomization
- Major surgery within 28 days prior to start of study treatment (diagnostic biopsy, laparotomy, line placement is not considered as major surgery)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction in the past 12 months, active gastrointestinal bleeding, central nervous system disorders or psychiatric illness/social situation that would limit compliance with study requirements or judged to be ineligible for the study by the investigator
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 |
|---|---|---|
| RegorafenibAlso: stivargaRegorafenib is administered at dose of 120 mg daily for 3 weeks in a 4-week cycle | Drug | Regorafenib, Regorafenib plus FOLFIRI |
| UGT1A1 genotyping (TA6/TA6)The dosage of irinotecan in FOLFIRI is escalated from 180mg/m2 to 260 mg/m2 | Genetic | Regorafenib plus FOLFIRI |
| UGT1A1 genotyping (TA6/TA7)The dosage of irinotecan in FOLFIRI is escalated from 180mg/m2 to 240 mg/m2 | Genetic | Regorafenib plus FOLFIRI |
| UGT1A1 genotyping (TA7/TA7)The dosage of irinotecan in FOLFIRI is escalated from 120mg/m2 to180 mg/m2 | Genetic | Regorafenib plus FOLFIRI |
| Leucovorin and 5-FULeucovorin (400 mg/m2 IV infusion over 2 hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period) | Drug | Regorafenib plus FOLFIRI |
Primary outcome
Progression-free survival
Time frame: From date of initiation of treatment until the date of first documented progression, assessed up to 23 months
Time from treatment to disease progresses and lives
5 secondary outcomes
Overall survival
Time frame: From date of initiation of treatment until the date of death from any cause, assessed up to 23 months
Best objective response
Time frame: From date of initiation of treatment until the date of disease progression, assessed up to 23 months
Disease control rate
Time frame: From date of initiation of treatment until the date of disease progression, assessed up to 23 months
Time to progression
Time frame: From date of initiation of treatment until the date of disease progression, assessed up to 23 months
Duration of treatment
Time frame: From date of initiation of treatment until the date of disease progression, assessed up to 23 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2019.
- Derived from this study: PubMed 41164204Huang CW, Chen YC, Ker TW, Lin YW, Chang TK, Su WC, Chen PJ, Tsai HL, Wang JY. Efficacy and safety of regorafenib plus FOLFIRI with UGT1A1 genotyping-guided irinotecan dose escalation against metastatic colorectal cancer: a multicenter, phase II, open-label, two-arm randomized controlled tria. Ther Adv Med Oncol. 2025 Oct 23;17:17588359251371489. doi: 10.1177/17588359251371489. eCollection 2025.
- Derived from this study: PubMed 31856912Ma CJ, Chang TK, Tsai HL, Su WC, Huang CW, Yeh YS, Chang YT, Wang JY. Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trial. Trials. 2019 Dec 19;20(1):751. doi: 10.1186/s13063-019-3917-z.
- 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.
Jaw-Yuan Wang, PhD study chair
Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Regorafenib, UGT1A1 genotyping (TA6/TA6) and UGT1A1 genotyping (TA6/TA7) in people with Metastatic Colorectal Cancer, run by Kaohsiung Medical University Chung-Ho Memorial Hospital at 1 site 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 20 inclusion and 13 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 21 Mar 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 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Jaw-Yuan Wang, PhD (+886-7-3122805, cy614112@ms14.hinet.net; jayuwa@cc.kmu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: From date of initiation of treatment until the date of first documented progression, assessed up to 23 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 NCT03880877, 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 21 Mar 2019.