Regorafenib Plus FOLFIRI With Irinotecan Dose Escalated in Patients With Previously Treated Metastatic Colorectal Cancer
1 other identifier
interventional
153
1 country
1
Brief 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 (mCRC).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2019
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 26, 2019
CompletedFirst Submitted
Initial submission to the registry
March 17, 2019
CompletedFirst Posted
Study publicly available on registry
March 19, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2021
CompletedMarch 21, 2019
March 1, 2019
2 years
March 17, 2019
March 19, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free survival
Time from treatment to disease progresses and lives
From date of initiation of treatment until the date of first documented progression, assessed up to 23 months
Secondary Outcomes (5)
Overall survival
From date of initiation of treatment until the date of death from any cause, assessed up to 23 months
Best objective response
From date of initiation of treatment until the date of disease progression, assessed up to 23 months
Disease control rate
From date of initiation of treatment until the date of disease progression, assessed up to 23 months
Time to progression
From date of initiation of treatment until the date of disease progression, assessed up to 23 months
Duration of treatment
From date of initiation of treatment until the date of disease progression, assessed up to 23 months
Study Arms (2)
Regorafenib plus FOLFIRI
EXPERIMENTALRegimen 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 COMPARATORRegorafenib is administered at adjusted dosage of 120 mg daily for 3 weeks in a 4-week cycle.
Interventions
Regorafenib is administered at dose of 120 mg daily for 3 weeks in a 4-week cycle
The dosage of irinotecan in FOLFIRI is escalated from 180mg/m2 to 260 mg/m2
The dosage of irinotecan in FOLFIRI is escalated from 180mg/m2 to 240 mg/m2
The dosage of irinotecan in FOLFIRI is escalated from 120mg/m2 to180 mg/m2
Leucovorin (400 mg/m2 IV infusion over 2 hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period)
Eligibility Criteria
You may qualify if:
- 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
- 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
- +5 more criteria
You may not qualify if:
- 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
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Chung-Ho Memorial Hospital, Kaohsiung Medical University:
Kaohsiung City, 807, Taiwan
Related Publications (2)
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.
PMID: 41164204DERIVEDMa 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.
PMID: 31856912DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Jaw-Yuan Wang, PhD
Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor, Vice Superintendent
Study Record Dates
First Submitted
March 17, 2019
First Posted
March 19, 2019
Study Start
February 26, 2019
Primary Completion
March 1, 2021
Study Completion
December 31, 2021
Last Updated
March 21, 2019
Record last verified: 2019-03
Data Sharing
- IPD Sharing
- Will not share