Phase I Study of Fruquintinib(HMPL-013) in Patients With Advanced Solid Tumors

NCT01645215 | Completed Phase 1 DMC

• 1 other identifier: 2009-013-00CH1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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 .

Conditions

Tumor

Outcome Measures

Primary Outcomes (1)

• Safety in the first 28-Days of Therapy

  The primary endpoint is evaluation of safety during the first 28-day cycle of therapy following the initiation of multiple dosing of HMPL-013. The safety variables to be evaluated in this study are adverse events, physical examinations, vital signs (specifically including blood pressure), clinical laboratory evaluations including serum chemistry, hematology , and urinalysis (with detailed sediment analysis, proteinuria, and 24-hour urine for collection for protein), and electrocardiograms (ECGs) in triplicate.

  28-Days after Permanent Discontinuation of HMPL-013

Secondary Outcomes (2)

• Objective Response Rate （ORR)

  every 8 weeks until end of treatment

• Pharmacokinetic Assessments for AUC, Cmax and Tmax

  Day 1-3 Single Dose and Day 1-28 Steady State

Study Arms (1)

Fruquintinib capsule

EXPERIMENTAL

cohort 1: fruquintinb continuous oral dosing (1mg once a day) cohort 2: fruquintinb continuous oral dosing (2mg once a day) cohort 3: fruquintinb continuous oral dosing (4mg once a day) cohort 4: fruquintinb continuous oral dosing (6mg once a day) cohort 5: fruquintinb continuous oral dosing (5mg once a day) cohort 6: fruquintinb oral dosing, 3 weeks on/1 week off (5mg once a day) cohort 7: fruquintinb oral dosing, 3 weeks on/1 week off (6mg once a day)

Drug: Fruquintinib

Interventions

Fruquintinib DRUG

Fruquintinib is a capsule in the form of 0.25mg , 1mg and 5mg, oral, once a day.

Also known as: HMPL-013

Fruquintinib capsule

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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead
• Fudan University: collaborator

Study Sites (1)

Fudan University Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Neoplasms

Interventions

HMPL-013

Study Design

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

Study Record Dates

• First Submitted: March 15, 2012
• First Posted: July 20, 2012
• Study Start: January 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: February 17, 2020

Record last verified: 2013-09

Locations

CN (1)