PMID- 31856912
OWN - NLM
STAT- MEDLINE
DCOM- 20200917
LR  - 20200917
IS  - 1745-6215 (Electronic)
IS  - 1745-6215 (Linking)
VI  - 20
IP  - 1
DP  - 2019 Dec 19
TI  - 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.
PG  - 751
LID - 10.1186/s13063-019-3917-z [doi]
LID - 751
AB  - BACKGROUND: Regorafenib is an oral multikinase inhibitor for metastatic 
      colorectal cancer (mCRC) previously treated with fluoropyrimidines, irinotecan, 
      oxaliplatin, monoclonal antibodies targeting vascular endothelial growth factor, 
      and monoclonal antibodies targeting epidermal growth factor receptor. A dose 
      reduction from 160 mg to 120 mg regorafenib reduces regorafenib-associated 
      adverse events (AEs). Dose adjustment of irinotecan in a 
      5-fluorouracil/leucovorin/irinotecan (FOLFIRI) regimen on the basis of an 
      individual uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotype 
      provides optimal oncological outcomes with acceptable AEs. The aim of this study 
      is to address the efficacy and safety of a dose-adjusted combination of 
      regorafenib and FOLFIRI for patients with mCRC. METHODS: 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 mCRC. The primary endpoint is 
      progression-free survival, and the secondary endpoints are overall survival, 
      disease control rate, time to progression, and duration of treatment. Safety 
      assessments will also be recorded. DISCUSSION: Dose adjustment for regorafenib 
      and irinotecan makes treatment-related AEs tolerable and makes the concomitant 
      treatment practicable. This study will provide initial evidence regarding the 
      efficacy and safety of a new combination of chemotherapy and a targeted agent for 
      mCRC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03880877. Prospectively 
      registered on 19 March 2019.
FAU - Ma, Cheng-Jen
AU  - Ma CJ
AD  - Division of Digestive and General Surgery, Department of Surgery, Kaohsiung 
      Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, 
      Kaohsiung, 807, Taiwan.
FAU - Chang, Tsung-Kun
AU  - Chang TK
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, 
      Kaohsiung, 807, Taiwan.
AD  - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung, Taiwan.
FAU - Tsai, Hsiang-Lin
AU  - Tsai HL
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, 
      Kaohsiung, 807, Taiwan.
AD  - Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung 
      Medical University, Kaohsiung, Taiwan.
FAU - Su, Wei-Chih
AU  - Su WC
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, 
      Kaohsiung, 807, Taiwan.
AD  - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung, Taiwan.
FAU - Huang, Ching-Wen
AU  - Huang CW
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, 
      Kaohsiung, 807, Taiwan.
AD  - Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung 
      Medical University, Kaohsiung, Taiwan.
FAU - Yeh, Yung-Sung
AU  - Yeh YS
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, 
      Kaohsiung, 807, Taiwan.
AD  - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung, Taiwan.
AD  - Division of Trauma and Surgical Critical Care, Department of Surgery, Kaohsiung 
      Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
FAU - Chang, Yu-Tang
AU  - Chang YT
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, 
      Kaohsiung, 807, Taiwan.
AD  - Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung 
      Medical University, Kaohsiung, Taiwan.
AD  - Division of Pediatric Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
FAU - Wang, Jaw-Yuan
AU  - Wang JY
AUID- ORCID: 0000-0002-7705-2621
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, 
      Kaohsiung, 807, Taiwan. cy614112@ms14.hinet.net.
AD  - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung, Taiwan. cy614112@ms14.hinet.net.
AD  - Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung 
      Medical University, Kaohsiung, Taiwan. cy614112@ms14.hinet.net.
AD  - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung, Taiwan. cy614112@ms14.hinet.net.
AD  - Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan. 
      cy614112@ms14.hinet.net.
LA  - eng
SI  - ClinicalTrials.gov/NCT03880877
GR  - MOST107-2321-B-037-003, MOST107-2314-B-037-023-MY2/Ministry of Science and 
      Technology, Taiwan/
GR  - KMUH98-8G05, KMUH107-7R28, KMUH107-7R29, KMUH107-7R30, KMUH107-7M22, 
      KMUH107-7M23/Kaohsiung Medical University Chung-Ho Memorial Hospital/
GR  - Biosignature in Colorectal Cancers/Academia Sinica/
PT  - Clinical Trial Protocol
PT  - Journal Article
DEP - 20191219
PL  - England
TA  - Trials
JT  - Trials
JID - 101263253
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Prodrugs)
RN  - 0 (Pyridines)
RN  - 24T2A1DOYB (regorafenib)
RN  - 7673326042 (Irinotecan)
RN  - EC 2.4.1.- (UGT1A1 enzyme)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
RN  - XT3Z54Z28A (Camptothecin)
RN  - IFL protocol
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Camptothecin/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Clinical Trials, Phase II as Topic
MH  - Colorectal Neoplasms/*drug therapy/genetics/mortality
MH  - Disease Progression
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Fluorouracil/administration & dosage/adverse effects/pharmacokinetics
MH  - Genotyping Techniques
MH  - Glucuronosyltransferase/*genetics
MH  - Humans
MH  - Irinotecan/*administration & dosage/adverse effects/pharmacokinetics
MH  - Leucovorin/administration & dosage/adverse effects/pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Multicenter Studies as Topic
MH  - Phenylurea Compounds/*administration & dosage/adverse effects/pharmacokinetics
MH  - Precision Medicine/adverse effects/methods
MH  - Prodrugs/administration & dosage/adverse effects/pharmacokinetics
MH  - Progression-Free Survival
MH  - Pyridines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Randomized Controlled Trials as Topic
MH  - Time Factors
MH  - Young Adult
PMC - PMC6923824
OTO - NOTNLM
OT  - Dose escalation
OT  - FOLFIRI
OT  - Metastatic colorectal cancer
OT  - Regorafenib
OT  - UGT1A1
COIS- The authors declare that they have no competing interests.
EDAT- 2019/12/21 06:00
MHDA- 2020/09/18 06:00
PMCR- 2019/12/19
CRDT- 2019/12/21 06:00
PHST- 2019/05/31 00:00 [received]
PHST- 2019/11/18 00:00 [accepted]
PHST- 2019/12/21 06:00 [entrez]
PHST- 2019/12/21 06:00 [pubmed]
PHST- 2020/09/18 06:00 [medline]
PHST- 2019/12/19 00:00 [pmc-release]
AID - 10.1186/s13063-019-3917-z [pii]
AID - 3917 [pii]
AID - 10.1186/s13063-019-3917-z [doi]
PST - epublish
SO  - Trials. 2019 Dec 19;20(1):751. doi: 10.1186/s13063-019-3917-z.