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A Phase Ib Study of Fruquintinib in 3rd Line mCRC

Primary Purpose

Colorectal Cancer

Status

Completed

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

fruquintinib

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring patients with mCRC who failed 2nd therapy or more

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Sun Yat-sen University Cancer Center
Fudan University Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

A- 4mg QD

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

Arm Description

arm A- fruquintinib 4mg once daily, p.o.,continuous;given in 28-days cycles until disease progress, intolerable toxicity or patients withdrawal of consent

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

objective response rate(ORR)

using RECIST version 1.1

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.

disease control rate (DCR)

using RECIST version 1.1

progression-free survival (PFS)

using RECIST version 1.1

overall survival (OS)

from first dosing until death due to any cause, assessed up to 2 years

Full Information

NCT ID

NCT01975077

First Posted

September 29, 2013

Last Updated

February 13, 2020

Sponsor

Hutchison Medipharma Limited

Collaborators

Fudan University, Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT01975077

Brief Title

A Phase Ib Study of Fruquintinib in 3rd Line mCRC

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2019

Overall Recruitment Status

Completed

Study Start Date

December 2012 (undefined)

Primary Completion Date

April 2014 (Actual)

Study Completion Date

October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hutchison Medipharma Limited

Collaborators

Fudan University, Sun Yat-sen University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer

Keywords

patients with mCRC who failed 2nd therapy or more

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

62 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A- 4mg QD

Arm Type

Experimental

Arm Description

arm A- fruquintinib 4mg once daily, p.o.,continuous;given in 28-days cycles until disease progress, intolerable toxicity or patients withdrawal of consent

Arm Title

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

Arm Type

Experimental

Arm Description

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 Type

Drug

Intervention Name(s)

fruquintinib

Other Intervention Name(s)

HMPL-013

Intervention Description

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

Primary Outcome Measure Information:

Title

safety and tolerability

Description

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

Time Frame

from day 1 of first dosing to 30days after permanent discontinuation of HMPL-013

Secondary Outcome Measure Information:

Title

objective response rate(ORR)

Description

using RECIST version 1.1

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

Title

pharmacokinetic profiles

Description

Time Frame

Day 1-84 steady state

Title

disease control rate (DCR)

Description

using RECIST version 1.1

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

Title

progression-free survival (PFS)

Description

using RECIST version 1.1

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

Title

overall survival (OS)

Description

from first dosing until death due to any cause, assessed up to 2 years

Time Frame

every 2 months since end of treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

Sun Yat-sen University Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

Facility Name

Fudan University Cancer Center

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200032

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

28103904

Citation

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.

Results Reference

derived

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A Phase Ib Study of Fruquintinib in 3rd Line mCRC

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