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TumorPhase 1HMPL-504NCT01773018

Phase I Study of the Volitinib (HMPL-504) in Patients With Advanced Solid Tumors

A Phase 1 study testing Volitinib in people with Tumor, run by Hutchison Medipharma Limited at 3 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Tumor
What is being tested?
Volitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
3 sitesAustralia
Study dates
Feb 2012to May 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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）.
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  • 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.

Trial locations and contacts

3 sites in 1 country.

Australia3 sites

  • Southern Health and Monash Institute of Medical Research

    Clayton, 3168

  • Austin Health

    Melbourne, 3084

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

Other trials in Australia

About this study

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

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.

Read the detailed description

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.

Conditions
Tumor
Being tested
Volitinib
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VolitinibDrug

    Also called HMPL-504

    Volitinib(HMPL-504) is a tablet in the form of 25 mg ,100mgand 200 mg,oral,once daily.

Study groups in NCT01773018
Study groupRoleWhat they receive
Volitinib(HMPL-504)ExperimentalThere 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).
Receives: Drug: Volitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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).

    Measured: up to 20 months

Secondary outcomes (1)

  1. Pharmacokinetic Assessments for area under curve (AUC), Cmax and Tmax .

    In the study of single-dose, full Pharmacokinetics(PK) profiles of HMPL-504 will be obtained following administration of a single oral dose of HMPL-504 on Day 1 to Day 3. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5,2,4,6,8 hour time points on days 1,15,21of dosing in the first 21-Day cycle of therapy, and pre-dose on days 2,8,16,and 22 of the first 21-Day cycle of therapy

    Measured: Day 1-3 Single Dose and Day 1-21 Steady State

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jan 2013 (estimated)
  2. Study startFeb 2012
  3. Primary completionDec 2015
  4. Study completionMay 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01773018
Sponsor's protocol ID
2011-504-00AU1
Acronym
HMPL-504
Status last verified
May 2016
First submitted
15 Jan 2013
Last updated
1 Jun 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Volitinib in people with Tumor, run by Hutchison Medipharma Limited at 3 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The safety and tolerability of single and multiple doses of HMPL-504 administered to patients. (time frame: up to 20 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01773018.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2016.

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