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

NCT01773018 | Completed Phase 1

• 1 other identifier: 2011-504-00AU1
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 3

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.

Conditions

Tumor

Outcome Measures

Primary Outcomes (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).

  up to 20 months

Secondary Outcomes (1)

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

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

Other Outcomes (1)

• Objective Response Rate （ORR)

  participants will be followed for the duration of hospital stay,an expected average of 3 months.

Study Arms (1)

Volitinib(HMPL-504)

EXPERIMENTAL

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).

Drug: Volitinib

Interventions

Volitinib DRUG

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

Also known as: HMPL-504

Volitinib(HMPL-504)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead
• Sir Charles Gairdner Hospital: collaborator
• Austin Hospital, Melbourne Australia: collaborator
• Monash University: collaborator

Study Sites (3)

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Southern Health and Monash Institute of Medical Research

Clayton, 3168, Australia

Location

Austin Health

Melbourne, 3084, Australia

Location

MeSH Terms

Conditions

Neoplasms

Interventions

1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine

Study Officials

• Michael Millward, MD,Ph.D

  Sir Charles Gairdner Hospital & University of WA

  PRINCIPAL INVESTIGATOR

• Hui Gan, MD,Ph.D

  Austin Hospital, Melbourne Australia

  PRINCIPAL INVESTIGATOR

• Jason Lickliter, MD,Ph.D

  Southern Health and Monash Institute of Medical Research

  PRINCIPAL INVESTIGATOR

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: January 15, 2013
• First Posted: January 21, 2013
• Study Start: February 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: May 1, 2016
• Last Updated: June 1, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)