Colorectal Cancer
Conditions
Keywords
patients with mCRC who failed 2nd therapy or more
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.
Interventions
DRUGfruquintinib
Fruquintinib is a capsule in the form of 1mg and 5mg, orally, daily
Sponsors
Fudan University
Sun Yat-sen University
Hutchison Medipharma Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| safety and tolerability | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | using RECIST version 1.1 |
| pharmacokinetic profiles | 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) | 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) | 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) | every 2 months since end of treatment | from first dosing until death due to any cause, assessed up to 2 years |
Countries
China
Outcome results
None listed