Clinical Trials /

Study of Metatinib Tromethamine Tablet

NCT02650375

Description:

This is an open-label, multicenter study designed to assess the safety, tolerability, preliminary efficacy and pharmacokinetics of Metatinib Tromethamine tablet in patients with advanced or metastatic gastric cancer, liver cancer, colorectal cancer,or con squamous NSCLC. Patients receive Metatinib orally 200mg once daily (QD) or 100mg twice daily (BID) until disease progression or unacceptable toxicity occurred. The study will determine whether MET gene mutation, amplification, as well as MET protein overexpression in tumor tissue correlate with treatment efficacy and clinical outcome. The potential PD biomarker for Metatinib will also be explored.

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

Unknown status

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Metatinib Tromethamine Tablet
  • Official Title: A Phase Ib Clinical Study of the Tolerance, Safety and Preliminary Efficacy Observation of Single-/Multiple- Doses of Metatinib Tromethamine Tablets in Patients With Advanced or Metastatic Solid Tumor

Clinical Trial IDs

  • ORG STUDY ID: SIM-128-I-02
  • NCT ID: NCT02650375

Conditions

  • Advanced or Metastatic Gastric Cancer
  • Advanced or Metastatic Liver Cancer
  • Advanced or Metastatic CRC
  • Advanced or Metastatic Non Squamous NSCLC

Interventions

DrugSynonymsArms
Metatinib TromethamineMetatinib Tromethamine

Purpose

This is an open-label, multicenter study designed to assess the safety, tolerability, preliminary efficacy and pharmacokinetics of Metatinib Tromethamine tablet in patients with advanced or metastatic gastric cancer, liver cancer, colorectal cancer,or con squamous NSCLC. Patients receive Metatinib orally 200mg once daily (QD) or 100mg twice daily (BID) until disease progression or unacceptable toxicity occurred. The study will determine whether MET gene mutation, amplification, as well as MET protein overexpression in tumor tissue correlate with treatment efficacy and clinical outcome. The potential PD biomarker for Metatinib will also be explored.

Trial Arms

NameTypeDescriptionInterventions
Metatinib TromethamineExperimental
  • Metatinib Tromethamine

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with advanced or metastatic gastric cancer or colorectal cancer who progress
             after second-line therapy or the above treatment protocol, or patients with advanced
             or metastatic hepatocellular carcinoma who progress after first-line chemotherapy,
             interventional therapy or targeted therapy shall be verified by histology or cytology;
             or patients with advanced or metastatic non-squamous non-small cell lung cancer who
             cannot be operated or fail to first-line therapy shall be verified by histology or
             cytology;

          -  MET gene amplification or protein overexpression(IHC ≥2+),or exon-14 skipping;

          -  At least one measurable lesion (RECIST 1.1 );

          -  At least 4 weeks from the last chemotherapy, radiotherapy or anti-tumor biological
             products treatment; at least 8 weeks from the last anti-tumor antibody products
             treatment; at least 6 weeks from the last dose of nitrosourea, mitomycin C or
             doxorubicin;

          -  At least 4 weeks from major surgery or trauma, and the wound should fully heal; at
             least 1 week from minor surgery or trauma (i.e. tissue biopsy or fine needle
             aspiration);

          -  Toxicity from previous treatment has to restore to ≤ grade 1, baseline or irreversible
             (NCI CTC4.0);

          -  ECOG performance status 0-1;

          -  Life expectancy ≥3 months;

          -  Adequate hematologic function: ANC≥1.5×10^9 /L, HB≥90g/L(blood transfusion allowed),
             PLT≥100×10^9/L;

          -  Adequate hepatic function: ALT≤3×ULN, AST≤3×ULN, TBIL≤2×ULN(patients with liver
             metastases or liver cancer ALT≤5×ULN, AST≤5×ULN, TBIL≤2×ULN), Child-Pugh score≤7;

          -  Adequate renal function: uric acid<500μmol/L, creatinine<1.7mg/dL,
             proteinuria≤2+or≤2g/24h , GFR≥60 ml/min/1.73m^2;

          -  PT-INR/APTT≤1.5×ULN, Serum sodium, potassium, calcium, magnesium levels ≤1×ULN(NCI-CTC
             4.0);

          -  Patients signed written informed consent;

          -  Willingness and capability to comply with protocol requirement and well communicate
             with investigators.

        Exclusion Criteria:

          -  Severe, uncontrolled medical disorders or active infection, including but not limited
             to HIV antibody positive, active tuberculosis, HBV DNA copies>10^3/ml;

          -  Subjects have known or suspected brain metastases;

          -  Patients must receive other chemotherapy, targeted therapy, hormone therapy,
             immunotherapy, radiotherapy (except for palliative local radiation) or traditional
             Chinese medicine for treatment of cancer during the study;

          -  Previously received other VEGF/VEGFR small-molecule inhibitors or antibodies therapy,
             including but not limited to Bevacizumab, Ramucirumab, Aflibercept;

          -  Previously received other HGF/c-Met small-molecule inhibitors or antibodies therapy,
             including but not limited to Crizotinib, Cabozantinib, Volitinib, Capmatinib (INC280),
             BPI-9016M;

          -  Imaging showed involvement of major blood vessels or nerves by tumor;

          -  Uncontrolled hypertension (systolic blood pressure>150mmHg and/or diastolic blood
             pressure>100mmHg after treatment);

          -  LVEF<50%;

          -  Apparent heart disease, including congestive heart failure(NYHA III-IV), history of
             myocardial infarction, or uncontrolled angina within 6 months prior to enrollment;

          -  Arrhythmias need to be treated, including atrial fibrillation, supraventricular
             tachycardia, ventricular tachycardia or ventricular fibrillation; ECG abnormalities
             confirmed, including QT interval prolongation (males>450msec, females>470 msec);

          -  History of hemorrhagic or thrombotic events within 6 months before enrollment, i.e.
             cerebrovascular accidents(including TIA), pulmonary embolism, spontaneous hemorrhage
             of tumor;

          -  Patients need surgery within 28 days, or is expected to require surgery within 28 days
             after the last dose;

          -  Uncontrolled cavity effusion, such as large amount of pleural effusion and ascites;

          -  Gastrointestinal illnesses(i.e., uncontrolled diarrhea or malabsorption) at screening
             or within 3 months that may affect drug absorption;

          -  History or suspicious signs of gastrointestinal perforation;

          -  Concomitant medications that may affect the drug metabolism (i.e. strong CYP3A4
             inhibitors or inducer );

          -  Pregnant or lactating women;

          -  Subjects of childbearing refused to use medically acceptable methods of contraception
             until 3 months after the last dose;

          -  Participate in other clinical trials within 4 weeks prior to enrollment;

          -  The investigators consider the patients are not suitable for this trial
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:incidence of adverse events
Time Frame:until 30 days after the last dose
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective response rate
Time Frame:every 6 weeks, up to 2 years
Safety Issue:
Description:
Measure:Disease control rate
Time Frame:every 6 weeks, up to 2 years
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:every 6 weeks, up to 2 years
Safety Issue:
Description:
Measure:Overall survival
Time Frame:every 6 weeks, up to 2 years
Safety Issue:
Description:
Measure:Cmax for Metatinib
Time Frame:day 1,day 2,day 8,day15,day22
Safety Issue:
Description:
Measure:Cmin for Metatinib
Time Frame:day 1,day 2,day 8,day15,day22
Safety Issue:
Description:
Measure:Tmax for Metatinib
Time Frame:day 1,day 2,day 8,day15,day22
Safety Issue:
Description:
Measure:AUC for Metatinib
Time Frame:day 1,day 2,day 8,day15,day22
Safety Issue:
Description:
Measure:T1/2 for Metatinib
Time Frame:day 1,day 2,day 8,day15,day22
Safety Issue:
Description:
Measure:CL for Metatinib
Time Frame:day 1,day 2,day 8,day15,day22
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jiangsu Simcere Pharmaceutical Co., Ltd.

Last Updated

January 20, 2017