A Phase Ib Study of Fruquintinib in 3rd Line mCRC

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fruquintinib

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: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: fruquintinib; Fruquintinib is a capsule in the form of 1mg and 5mg, orally, daily; Other Names: HMPL-013
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	Drug: fruquintinib; Fruquintinib is a capsule in the form of 1mg and 5mg, orally, daily; Other Names: HMPL-013

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety and tolerability	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	from day 1 of first dosing to 30days after permanent discontinuation of HMPL-013

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate(ORR)	using RECIST version 1.1	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
pharmacokinetic profiles	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.	Day 1-84 steady state
disease control rate (DCR)	using RECIST version 1.1	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 survival (PFS)	using RECIST version 1.1	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
overall survival (OS)	from first dosing until death due to any cause, assessed up to 2 years	every 2 months since end of treatment

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited
• Collaborators: Sun Yat-sen University; Fudan University

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: September 29, 2013
• First Submitted That Met QC Criteria: October 28, 2013
• First Posted (Estimate): November 3, 2013

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: patients with mCRC who failed 2nd therapy or more
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 2012-013-00CH3