Phase I Clinical Study of Metatinib Tromethamine Tablet

NCT02004548 | Completed Phase 1

• 1 other identifier: SIM-89-1
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To evaluate the safety, tolerability and maximum tolerated dose (MTD) of daily oral administration of metatinib tromethamine in subjects with solid tumors; Investigate the influence of food on pharmacokinetic parameters. Secondary Objective: To evaluate the plasma pharmacokinetics (PK) of daily oral administration of metatinib tromethamine in subjects with solid tumors; To observe preliminary anti-tumor efficacy; To evaluate potential pharmacodynamic and predictive biomarkers at MTD.

Conditions

Advanced or Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Dose-limiting Toxicity (DLT)

  up to day 32

• Maximum Tolerated Dose (MTD)

  up to day 32

Secondary Outcomes (3)

• Cmax

  d1、d2、d3、d8、d15、d22、d29、d30、d31

• AUC

  d1、d2、d3、d8、d15、d22、d29、d30、d31

• Objective response rate (ORR)

  week 4, week 10, week 16

Study Arms (1)

Metatinib Tromethamine

EXPERIMENTAL

Dose escalation is in accordance with the traditional "3 +3" design, and dose groups are subsequently set as: 25, 50, 100, 200, 300, 450, 600, 800 mg/d.

Drug: Metatinib Tromethamine

Interventions

Metatinib Tromethamine DRUG

Metatinib Tromethamine

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Weight: male weight ≥ 45 kg; female weight ≥ 40 kg, body mass index (BMI) between 18\~24 kg/m\^2, including the boundary values;
• The subject has a histologically confirmed solid tumor that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no known therapies to prolong survival;
• Not treated with standard therapeutical regime currently, or has progressed or relapsed after standard treatment;
• Time from last cytotoxic chemotherapy (including investigational cytotoxic agents) or biologic agents (immune modulators, cytokines) ≥ 4 weeks, or nitrosoureas or mitomycin C ≥ 6 weeks. If having received an antibody anti-tumor biological product, at least 8-week washout period is required;
• At least 4 weeks after surgery, and the wound must be healed completely;
• If subject has chemotherapy-induced toxicity, the adverse events must be recovered to ≤ grade 1 (NCI-CTC version 4.0) except for alopecia;
• ECOG performance status of 0-2;
• Expected survival time is more than three months;
• The subject has organ and marrow function as follows:
• absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L,
• platelets ≥ 80 x 10\^9/L,
• hemoglobin ≥ 90 g/L (blood transfusion is allowed),
• total bilirubin ≤ 2 x ULN (\<3 x ULN with liver metastases),
• serum creatinine ≤ 150 μmol/L or calculated creatinine clearance ≥ 60 mL/min,
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN (\<5 x ULN with liver metastases),

You may not qualify if:

• The subject is known to be positive for the human immunodeficiency virus (HIV);
• The subject is known to be positive for hepatitis B surface antigen or hepatitis C;
• Previous participation in other clinical trials within three months before study;
• Concomitant chemotherapy, hormone therapy, immunotherapy program or radiotherapy;
• The subject has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia;
• The subject has psychiatric illness/social situations that would limit compliance with study requirements;
• The subject has brain metastases;
• Imaging study showed involvement of major blood vessels or nerves by tumor;
• Uncontrollable hypertension (referring to systolic blood pressure\> 150 mmHg and / or diastolic blood pressure\> 100 mmHg after treatment) or LVEF \<50%;
• Patient with disease history of bleeding or thromboembolic events occurred within the past six months and need for preventive anticoagulant therapy;
• Patient needs surgery within 28 days, or is expected to require surgery within 28 days after the last dose administration;
• Significant abnormality in the important organs, such as heart, lung, liver, kidney;
• Has third lacunar effusion with difficulty to control;
• The subject is pregnant or breastfeeding;
• Sexually active subjects (male and female) refuse to use medically acceptable methods of contraception during the course of the study and for 1 month following discontinuation of study drug.

Sponsors & Collaborators

• Jiangsu Simcere Pharmaceutical Co., Ltd.: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Location

Related Publications (1)

• Tabouret E, Fabbro M, Autran D, Hoang-Xuan K, Taillandier L, Ducray F, Barrie M, Sanson M, Kerr C, Cartalat-Carel S, Loundou A, Guillevin R, Mokhtari K, Figarella-Branger D, Delattre JY, Chinot O. TEMOBIC: Phase II Trial of Neoadjuvant Chemotherapy for Unresectable Anaplastic Gliomas: An ANOCEF Study. Oncologist. 2021 Aug;26(8):647-e1304. doi: 10.1002/onco.13765. Epub 2021 Apr 20.

  PMID: 33783067 DERIVED

Study Officials

• Feng Bi, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

• Maozhi Liang, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

• You Lu, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

• Qin Yu, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

• Li Zheng, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2013
• First Posted: December 9, 2013
• Study Start: May 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 29, 2015

Record last verified: 2015-11

Locations

CN (1)