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

Jiangsu Simcere Pharmaceutical Co., Ltd.3 sites in 1 country24 target enrollmentOctober 2015

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

InterventionsMetatinib Tromethamine

DrugsMetatinib Tromethamine

Overview

Phase: Phase 1
Intervention: Metatinib Tromethamine
Conditions: Advanced or Metastatic Gastric Cancer
Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Enrollment: 24
Locations: 3
Primary Endpoint: incidence of adverse events
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

October 2015

End Date

February 2018

Last Updated

9 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Jiangsu Simcere Pharmaceutical Co., Ltd.

Responsible Party

Sponsor

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;

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);