Clinical Trials /

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

NCT01985555

Description:

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).

Related Conditions:
  • Gastric Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 2011-504-00CH1
  • NCT ID: NCT01985555

Conditions

  • Tumors

Interventions

DrugSynonymsArms
Volitinib(HMPL-504)Volitinib(HMPL-504)

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
Volitinib(HMPL-504)ExperimentalThere are 5 dose cohorts,including600 QD,800QD and 400BID mg,500BID in the dose escalation stage and HMPL-504 will be administered orally to patients once daily for each dose cohort., in the dose expansion stage 500BID will be administered orally to patients.
  • Volitinib(HMPL-504)

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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).
Time Frame:up to 20 months
Safety Issue:
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).

Secondary Outcome Measures

Measure:Pharmacokinetic Assessments for area under curve (AUC), Cmax and Tmax .
Time Frame:Day 1-3 Single Dose and Day 1-21 Steady State
Safety Issue:
Description: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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hutchison Medipharma Limited

Trial Keywords

  • Phase I
  • Safety
  • Pharmacokinetics

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