Clinical trial NCT01975077: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Keywords: patients with mCRC who failed 2nd therapy or more
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
Collaborators: name: Fudan University
name: Sun Yat-sen University
First posted: 2013-11-03
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: safety and tolerability
timeFrame: from day 1 of first dosing to 30days after permanent discontinuation of HMPL-013
Secondary outcomes:
measure: objective response rate(ORR)
timeFrame: 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
measure: pharmacokinetic profiles
timeFrame: Day 1-84 steady state
measure: disease control rate (DCR)
timeFrame: 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
measure: progression-free survival (PFS)
timeFrame: 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
measure: overall survival (OS)
timeFrame: every 2 months since end of treatment
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Shanghai
country: China
facility: Fudan University Cancer Center
state: Shanghai
Study officials:
References:
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.