Clinical trial NCT01645215: Phase I Study of Fruquintinib(HMPL-013) in Patients With Advanced Solid Tumors
Official title: Phase I Study of Safety and Pharmacokinetics of Fruquintinib(HMPL-013) in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tumor
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
Collaborators: name: Fudan University
First posted: 2012-07-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Fruquintinib (HMPL-013) is a novel oral small molecule that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and has demonstrated potent inhibitory effects on multiple human tumor xenografts. This first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics , safety and preliminary anti-tumor activity of HMPL-013 at single doses and multiple doses .

Detailed description: This will be an open-label, phase I study. This study will evaluate the safety and pharmacokinetics of HMPL-013 after a single administration followed by a 28-Day continuous course of therapy; evaluate the safety and preliminary efficacy in an open-label administration of at the MTD. All subjects of this study will be permitted to continue therapy with only safety monitoring and bimonthly assessments for progression, if the product is well tolerated and the subject has stable disease or better.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 and ≤ 70 years of age
* Histological or cytological confirmed solid malignant tumor
* ECOG performance status of 0-1
* Standard regimen failed or no standard regimen available
* Life expectancy of more than 12 weeks
* LVEF ≥ 50%
* Duration from the last therapy is more than 4 weeks for operation or radiotherapy; more than 4 weeks for prior systemic treatment
* Adequate hepatic, renal, heart, and hematologic functions (platelets \> 80 × 109/L, neutrophil \> 1.5 × 109/L, hemoglobin \> 90g/dl ,serum creatinine within upper limit of normal(ULN), total bilirubin and serum transaminase within upper limit of normal(ULN), and PT, APTT, TT, Fbg normal
* 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 uncontrolled 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 VEGF/VEGFR inhibition
* Disability of serious uncontrolled intercurrence infection
* Proteinuria ≥ 2+
* 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 in the first 28-Days of Therapy
timeFrame: 28-Days after Permanent Discontinuation of HMPL-013
Secondary outcomes:
measure: Objective Response Rate （ORR)
timeFrame: every 8 weeks until end of treatment
measure: Pharmacokinetic Assessments for AUC, Cmax and Tmax
timeFrame: Day 1-3 Single Dose and Day 1-28 Steady State
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Cancer Center
state: Shanghai
Study officials:
References: