A Phase Ib Study of Fruquintinib in 3rd Line mCRC

NCT01975077 | Completed Phase 1 DMC

• 1 other identifier: 2012-013-00CH3
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 2

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.

Conditions

Colorectal Cancer

Keywords

patients with mCRC who failed 2nd therapy or more

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• objective response rate(ORR)

  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

  Day 1-84 steady state

• disease control rate (DCR)

  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)

  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)

  every 2 months since end of treatment

Study Arms (2)

A- 4mg QD

EXPERIMENTAL

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

B- 5mg once daily, 3wks on/1wk off

EXPERIMENTAL

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

Interventions

fruquintinib DRUG

Fruquintinib is a capsule in the form of 1mg and 5mg, orally, daily

Also known as: HMPL-013

A- 4mg QD; B- 5mg once daily, 3wks on/1wk off

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead
• Fudan University: collaborator
• Sun Yat-sen University: collaborator

Study Sites (2)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Fudan University Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

Related Publications (1)

• 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.

  PMID: 28103904 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2013
• First Posted: November 4, 2013
• Study Start: December 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: October 1, 2014
• Last Updated: February 17, 2020

Record last verified: 2019-02

Locations

CN (2)