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A Phase I, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of HMPL-504 in Patients With Advanced Solid Tumors

Phase 1
18 Years
Open (Enrolling)

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Trial Information

A Phase I, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of HMPL-504 in Patients With Advanced Solid Tumors

This is a Phase I, first-in-human, open-label, dose-escalation study of Volitinib (HMPL-504)
administered orally once every day(QD) to patients with locally advanced or metastatic solid
tumors.There are two stages to this study : a dose-escalation stage and a dose-expansion
stage. The dose-escalation stage is designed to evaluate the safety, tolerability, and
pharmacokinetics of single dose and repeat doses of HMPL-504 given once every day (QD). An
alternative dosing schedule of twice every day (BID) may be investigated if pharmacokinetic
studies indicate faster than anticipated clearance of HMPL-504.

All patients will be carefully followed for adverse events during the study treatment and
for 30 days after the last dose of study drug. 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.

Inclusion Criteria:

- Signed Informed Consent Form

- Age≥18 years

- Histologically or cytologically documented, incurable, locally advanced, or
metastatic solid malignancy that has progressed on, or failed to respond to, at least
one prior systemic therapy

- Evaluable or measurable disease per Response Evaluation Criteria in Solid

- Eastern Cooperative Oncology Group (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

- In the dose expansion stage, the patient's informed consent to providing fresh biopsy
tumor sample at baseline and day 7 should be obtained. Patients with gastric cancer ,
NSCLC, colorectal cancer, breast cancer and hepatocellular carcinoma(HCC) are
preferred to be enrolled into the dose expansion cohort.

Exclusion Criteria:

• Inadequate hematologic and organ function, defined by the following (hematologic
parameters must be assessed ≥14 days after a prior treatment, if any):

- Absolute neutrophil count <1500 cells/L

- Hemoglobin <9 g/dL

- Total bilirubin >1.5 × the upper limit of normal (ULN) with the following exception:
Patients with known Gilbert disease who have

serum bilirubin level ≤3× the upper limit of normal(ULN) and normal AST/ALT may be

- Aspartate aminotransferase (AST) and/or Alanine transaminase(ALT) >2.5 × the upper
limit of normal(ULN) with the following exception: Patients with documented liver
metastases may have AST and/or ALT levels ≤5 ×the upper limit of normal(ULN).

- Serum creatinine >1.5 × the upper limit of normal (ULN) with the following exception:
A creatinine clearance of ≥50 mL/min based on a documented 24-hour urine collection.

- International normalized ratio (INR)>1.5× the ULN or activated partial thromboplastin
time (aPTT)>1.5×the ULN

- The INR applies only to patients who do not receive therapeutic anti-coagulation.

• Any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic
therapy, radiotherapy, or herbal therapy within 4 weeks prior to initiation of study
treatment with the following exceptions:

- Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists for prostate

- Hormone-replacement therapy or oral contraceptives

- Palliative radiation to bone metastases > 2 weeks prior to Day 1

- 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

- New York Heart Association (NYHA) Class II or greater congestive heart failure

- History of myocardial infarction or unstable angina within 6 months prior to Day

- History of stroke or transient ischemic attack within 6 months prior to Day 1

- Active or untreated brain metastasis

- Inability to take oral medication, prior surgical procedures affecting
absorption, or active peptic ulcer disease

- Inability to comply with study and follow-up procedures

- Any other diseases, metabolic dysfunction, physical examination finding, or
clinical laboratory finding that, in the investigator's opinion, gives
reasonable suspicion of a disease or condition that contraindicates the use of
an investigational drug or that may affect the interpretation of the results or
renders the patient at high risk from treatment complications.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The safety and tolerability of single and multiple doses of HMPL-504 administered to patients.

Outcome 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).

Outcome Time Frame:

up to 20 months

Safety Issue:


Principal Investigator

Michael Millward, MD,Ph.D

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sir Charles Gairdner Hospital & University of WA


Australia: Department of Health and Ageing Therapeutic Goods Administration

Study ID:




Start Date:

February 2012

Completion Date:

December 2013

Related Keywords:

  • Tumor