Clinical trial NCT01985555: Phase I Study of the Volitinib (HMPL-504) in Patients With Advanced Solid Tumors
Official title: A Phase I, Open-label, Multicenter Dose-escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of Volitinib in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tumors
Keywords: Phase I
Safety
Pharmacokinetics
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2013-11-15
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and tolerability of single and multiple doses of volitinib administered to patients with locally advanced or metastatic solid tumors and determine MTD (Maximum Tolerated Dose) or RPTD(recommended Phase 2 dose).

Detailed description: The primary endpoint is evaluation of safety and tolerability during all the study of therapy following the initiation of multiple dosing of HMPL-504. The safety and tolerability 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 (Maximum Tolerated Dose), and urinalysis (with detailed sediment analysis, proteinuria, and 24-hour urine for collection for protein), and electrocardiograms (ECGs) in triplicate, Incidence and nature of DLTs (Dose-Limiting Toxicity), to determine the MTD (Maximum Tolerated Dose).

Eligibility criteria: Inclusion Criteria:

* Signed Informed Consent Form
* Age≥18 years
* Histologically or cytologically documented(include both dose escalation stage and dose expansion stage), incurable, locally advanced, or metastatic solid malignancy
* In the dose escalation stage: patients with any malignant solid tumor type for whom standard therapy either has proven to be ineffective (progressed on, or failed to respond to) or intolerable, have no access to standard systemic therapy or standard systemic therapy does not exist.
* In the dose expansion stage:

Metastatic or locally advanced gastric cancer patients with cMet positive b)Metastatic or locally advanced EGFR wild type NSCLC patients and with cMet positive.

* ECOG performance status of 0, or 1
* Male or female patients of child-producing potential must agree to use double barrier contraception, condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD), contraceptives (oral or parenteral), Implanon, injectables or other avoidance of pregnancy measures during the study and for 90 days after the last day of treatment

Exclusion Criteria:

* Absolute neutrophil count \<1500 cells/uL, hemoglobin \<9 g/dL or platelet count \< 100,000/mm3
* Total bilirubin \> 1.5×the the upper limit of normal(ULN).
* Herbal therapy \<1 week prior to Day 1
* Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1, except for alopecia
* Clinical significant active infection
* Known clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
* Known human immunodeficiency virus infection
* Pregnant (positive pregnancy test) or lactating women
* Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease
* Involved in other clinical trials \< 4weeks prior to Day 1.

Primary outcomes:
measure: The primary endpoint is evaluation of safety and tolerability during all the study of therapy following the initiation of multiple dosing of Volitinib (HMPL-504).
timeFrame: up to 20 months
Secondary outcomes:
measure: Pharmacokinetic Assessments for area under curve (AUC), Cmax and Tmax .
timeFrame: Day 1-3 Single Dose and Day 1-21 Steady State
Other outcomes:
Locations:
city: Beijing
country: China
facility: BeijingCancer Hospital
state: Beijing
Study officials:
affiliation: Investigator
name: Lin Shen, MD.PHD
role: PRINCIPAL_INVESTIGATOR
References: