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A Phase Ib Study of Fruquintinib in 3rd Line mCRC

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ClinicalTrials.gov Identifier: NCT01975077
Recruitment Status : Completed
First Posted : November 3, 2013
Last Update Posted : February 17, 2020
Sponsor:
Collaborators:
Fudan University
Sun Yat-sen University
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Tracking Information
First Submitted Date  ICMJE September 29, 2013
First Posted Date  ICMJE November 3, 2013
Last Update Posted Date February 17, 2020
Study Start Date  ICMJE December 2012
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2013)
safety and tolerability [ Time Frame: from day 1 of first dosing to 30days after permanent discontinuation of HMPL-013 ]
The primary objective is evaluation of safety and tolerabilty with 2 regimens. The primary endpoint is the incidence of AEs, SAEs, Gr3/4 AEs and AEs led to dose interruption and dose discontinued
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2019)
  • objective response rate(ORR) [ Time Frame: every 8 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months ]
    using RECIST version 1.1
  • pharmacokinetic profiles [ Time Frame: Day 1-84 steady state ]
    At QD regimen, PK sampling will include a pre-dose and at the 1,2,4,8,24 hour time points on day 1 and day 21;a pre-dose and at the 2 hour time point on day 28,42,70,84. At 3wks on/1wk off regimen,PK sampling will include a pre-dose and at the 1,2,4,8,24 hour time points on day 1 and day 21; a pre-dose and at the 2 hour time point on day 42 and day 70; only pre-dose on day 28,56,84.
  • disease control rate (DCR) [ Time Frame: every 8 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months ]
    using RECIST version 1.1
  • progression-free survival (PFS) [ Time Frame: every 8 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months ]
    using RECIST version 1.1
  • overall survival (OS) [ Time Frame: every 2 months since end of treatment ]
    from first dosing until death due to any cause, assessed up to 2 years
Original Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2013)
  • efficacy (tumor assessment every 8 weeks till end of treatment) [ Time Frame: every 8 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months ]
    objective response rate(ORR)
  • efficacy [ Time Frame: every 8 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months ]
    disease control rate (DCR)
  • efficacy [ Time Frame: every 8 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months ]
    Progression-free suvival (PFS)
  • efficacy [ Time Frame: every 3 months until date of death from any cause, assessed up to 20 months ]
    overall survival (OS)
  • pharmacokinetic profiles [ Time Frame: Day 1-84 steady state ]
    At QD regimen, PK sampling will include a pre-dose and at the 1,2,4,8,24 hour time points on day 1 and day 21;a pre-dose and at the 2 hour time point on day 28,42,70,84. At 3wks on/1wk off regimen,PK sampling will include a pre-dose and at the 1,2,4,8,24 hour time points on day 1 and day 21; a pre-dose and at the 2 hour time point on day 42 and day 70; only pre-dose on day 28,56,84.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase Ib Study of Fruquintinib in 3rd Line mCRC
Official Title  ICMJE A Randomized, Open-label Phase Ib Trial of Fruquintinib "4mg Once Daily Continuous"Versus "5mg Once Daily 3wks on/1wk Off" in Patients With Metastatic Colorectal Carcinoma as 3rd Therapy
Brief Summary Fruquintinib is a novel oral small molecule compound discovered and developed by Hutchison MediPharma that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and has demonstrated potent inhibitory effects on multiple human tumor xenografts.Based on first-in-human study, both 4mg QD and 5mg 3wks on/1wk off are safety and efficacy, this phase Ib study is to evaluable the safety, tolerability and efficacy of these 2 regimens with mCRC failed 2nd therapy or more and to determine the recommended dose and regimen in phase II/III study.
Detailed Description

This is a phase Ib, randomize, interventional, open-label, multicenter study to provide fruquintinib to subjects diagnosed with metastatic colorectal cancer who have failed after standard therapy and for whom no therapy alternatives exist.

The primary endpoint of this study will be safety.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE Drug: fruquintinib
Fruquintinib is a capsule in the form of 1mg and 5mg, orally, daily
Other Name: HMPL-013
Study Arms  ICMJE
  • Experimental: A- 4mg QD
    arm A- fruquintinib 4mg once daily, p.o.,continuous;given in 28-days cycles until disease progress, intolerable toxicity or patients withdrawal of consent
    Intervention: Drug: fruquintinib
  • Experimental: B- 5mg once daily, 3wks on/1wk off
    arm B-fruquintinb 5mg once daily,p.o.,3 weeks on/1 week off, given in 28-day cycles until disease progress,intolerable toxicity or patients withdrawal of consent
    Intervention: Drug: fruquintinib
Publications * Xu RH, Li J, Bai Y, Xu J, Liu T, Shen L, Wang L, Pan H, Cao J, Zhang D, Fan S, Hua Y, Su W. Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study. J Hematol Oncol. 2017 Jan 19;10(1):22. doi: 10.1186/s13045-016-0384-9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 9, 2014)
62
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2013)
60
Actual Study Completion Date  ICMJE October 2014
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • ≥ 18 and ≤ 70 years of age , with ≥ 40Kg
  • Histological or cytological confirmed colorectal cancer
  • ECOG performance status of 0-1
  • Standard regimen failed or no standard regimen available
  • Adequate hepatic, renal, heart, and hematologic functions
  • At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan)
  • Signed and dated informed consent.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure

Exclusion Criteria:

  • Pregnant or lactating women
  • Any factors that influence the usage of oral administration
  • Evidence of CNS metastasis
  • Intercurrence with one of the following: non-controlled hypertension, coronary artery disease, arrhythmia and heart failure
  • Abuse of alcohol or drugs
  • Less than 4 weeks from the last clinical trial
  • Previous treatment with VEGFR inhibition
  • Disability of serious uncontrolled intercurrence infection
  • Proteinuria ≥ 2+ (1.0g/24hr)
  • Uncontrolled hemorrhage in GI
  • Within 12 months before the first treatment occurs artery/venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack) etc.
  • Within 6 months before the first treatment occurs acute myocardial infarction, acute coronary syndrome or CABG
  • Bone fracture or wounds that was not cured for a long time
  • Coagulation dysfunction, hemorrhagic tendency or receiving anticoagulant therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01975077
Other Study ID Numbers  ICMJE 2012-013-00CH3
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hutchison Medipharma Limited
Study Sponsor  ICMJE Hutchison Medipharma Limited
Collaborators  ICMJE
  • Fudan University
  • Sun Yat-sen University
Investigators  ICMJE Not Provided
PRS Account Hutchison Medipharma Limited
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP