Phase I Clinical Study of Metatinib Tromethamine Tablet

Advanced or Metastatic Solid Tumors Clinical Trial

Official title:

A Phase I, Multiple Dose Escalation Clinical Trial of Metatinib Tromethamine Tablet in Patients With Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02004548
• Other study ID #: SIM-89-1
• Status: Completed
• Phase: Phase 1
• First received: November 26, 2013
• Last updated: December 28, 2015
• Start date: May 2013
• Est. completion date: December 2015

Study information

• Verified date: November 2015
• Source: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• 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:

1. absolute neutrophil count (ANC) = 1.5 x 10^9/L,

2. platelets = 80 x 10^9/L,

3. hemoglobin = 90 g/L (blood transfusion is allowed),

4. total bilirubin = 2 x ULN (<3 x ULN with liver metastases),

5. serum creatinine = 150 µmol/L or calculated creatinine clearance = 60 mL/min,

6. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x ULN (<5 x ULN with liver metastases),

7. uric acid <500 µmol/L,

8. proteinuria = 2 + or = 2g / 24h;

• The subject is capable of understanding and complying with the protocol and has signed the informed consent document;

Exclusion Criteria:

• 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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors

Intervention

Drug:
• Metatinib Tromethamine

Locations

Country	Name	City	State
China	West China Hospital, Sichuan University	Chengdu	Sichuan

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	Dose-limiting Toxicity (DLT)		up to day 32	Yes
Primary	Maximum Tolerated Dose (MTD)		up to day 32	Yes
Secondary	Cmax		d1?d2?d3?d8?d15?d22?d29?d30?d31	No
Secondary	AUC		d1?d2?d3?d8?d15?d22?d29?d30?d31	No
Secondary	Objective response rate (ORR)		week 4, week 10, week 16	No