Study of Metatinib Tromethamine Tablet

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

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.

Study Overview

• Status: Unknown
• Conditions: Advanced or Metastatic Gastric Cancer; Advanced or Metastatic CRC; Advanced or Metastatic Liver Cancer; Advanced or Metastatic Non Squamous NSCLC
• Intervention / Treatment: Drug: Metatinib Tromethamine

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • The First Bethune Hospital of Jilin University
      • Contact: Yanhua Ding, MD
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Feng Bi, MD
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metatinib Tromethamine	Drug: Metatinib Tromethamine; Patients receive Metatinib orally 200mg once daily (QD) or 100mg twice daily (BID) until disease progression or unacceptable toxicity occurred.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
incidence of adverse events	until 30 days after the last dose

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Feng Bi, MD, West China Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): February 1, 2018

Study Registration Dates

• First Submitted: November 10, 2015
• First Submitted That Met QC Criteria: January 7, 2016
• First Posted (Estimate): January 8, 2016

Study Record Updates

• Last Update Posted (Estimate): January 23, 2017
• Last Update Submitted That Met QC Criteria: January 20, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: SIM-128-I-02