Study of Metatinib Tromethamine Tablet

Advanced or Metastatic Gastric Cancer Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT02650375
• Other study ID #: SIM-128-I-02
• Status: Recruiting
• Phase: Phase 1
• First received: November 10, 2015
• Last updated: January 20, 2017
• Start date: October 2015
• Est. completion date: February 2018

Study information

• Verified date: January 2017
• Source: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Contact: Shuangling Deng, MS
• Phone: 86-025-85560000
• Email: dengshuangling[@]simcere.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: February 2018
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Metatinib Tromethamine
Patients receive Metatinib orally 200mg once daily (QD) or 100mg twice daily (BID) until disease progression or unacceptable toxicity occurred.

Locations

Country	Name	City	State
China	The First Bethune Hospital of Jilin University	Changchun	Jilin
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	The First Affiliated Hospital, Zhejiang University	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Simcere Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	incidence of adverse events		until 30 days after the last dose
Secondary	Objective response rate		every 6 weeks, up to 2 years
Secondary	Disease control rate		every 6 weeks, up to 2 years
Secondary	Progression free survival		every 6 weeks, up to 2 years
Secondary	Overall survival		every 6 weeks, up to 2 years
Secondary	Cmax for Metatinib		day 1,day 2,day 8,day15,day22
Secondary	Cmin for Metatinib		day 1,day 2,day 8,day15,day22
Secondary	Tmax for Metatinib		day 1,day 2,day 8,day15,day22
Secondary	AUC for Metatinib		day 1,day 2,day 8,day15,day22
Secondary	T1/2 for Metatinib		day 1,day 2,day 8,day15,day22
Secondary	CL for Metatinib		day 1,day 2,day 8,day15,day22