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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01773018




Registration number
NCT01773018
Ethics application status
Date submitted
15/01/2013
Date registered
21/01/2013
Date last updated
1/06/2016

Titles & IDs
Public title
Phase I Study of the Volitinib (HMPL-504) in Patients With Advanced Solid Tumors
Scientific title
A Phase I, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of HMPL-504 in Patients With Advanced Solid Tumors
Secondary ID [1] 0 0
2011-504-00AU1
Universal Trial Number (UTN)
Trial acronym
HMPL-504
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Volitinib

Experimental: Volitinib(HMPL-504) - There are six dose cohorts,including 100, 200, 400, 600,800 and 1000 mg/day, HMPL-504 will be administered orally to patients once daily for each dose cohort.
An alternative dosing schedule of twice every day (BID) may be investigated if pharmacokinetic studies indicate faster than anticipated clearance of Volitinib(HMPL-504).


Treatment: Drugs: Volitinib
Volitinib(HMPL-504) is a tablet in the form of 25 mg ,100mgand 200 mg,oral,once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The safety and tolerability of single and multiple doses of HMPL-504 administered to patients.
Timepoint [1] 0 0
up to 20 months
Secondary outcome [1] 0 0
Pharmacokinetic Assessments for area under curve (AUC), Cmax and Tmax .
Timepoint [1] 0 0
Day 1-3 Single Dose and Day 1-21 Steady State

Eligibility
Key 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
Tumors(RECIST)

- 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 treatment

- 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
enrolled.

- 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
cancer

- 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
1

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2016
Sample size
Target
Accrual to date
Final
47
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 0 0
Southern Health and Monash Institute of Medical Research - Clayton
Recruitment hospital [3] 0 0
Austin Health - Melbourne
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3084 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hutchison Medipharma Limited
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Sir Charles Gairdner Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Austin Hospital, Melbourne Australia
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Monash University
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Volitinib (HMPL-504) is a novel, highly potent and selective small molecule inhibitor of
c-Met kinase. In preclinical studies, it demonstrated strong in vitro and in vivo activity
against c-Met kinase and its downstream signaling targets and inhibited tumor cell growth.
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-504 at single doses and multiple doses.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01773018
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Millward, MD,Ph.D
Address 0 0
Sir Charles Gairdner Hospital & University of WA
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01773018