Phase I Study of SHR7390 in Patients With Advanced Solid Tumors

NCT02968485 | Unknown Phase 1

• 1 other identifier: SHR7390-I-101-AST
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This aim of study to assess the safety and tolerability of SHR7390 and to define the maximum tolerated dose (MTD) of SHR7390 in the patients with advanced solid tumors. To evaluate the pharmacokinetics of SHR7390 in patients with advanced solid tumors. To study the effects of food on the pharmacokinetic parameters of SHR7390. To assess the antitumor activity of SHR7390 in patients with advanced solid tumors preliminarily and recommend reasonable dosage regimen for the follow-up clinical trial.

Conditions

Solid Tumor

Keywords

advanced solid tumor; Protein Kinase MEK inhibitor (MEKi); Safety; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  to assess safety and tolerability of SHR7390 with a maximum tolerated dose (MTD) of SHR7390 in patients with advanced solid tumors

  Day 1 to 28 ( Cycle 1)

Secondary Outcomes (20)

• The measurement of maximum plasma concentration (Cmax)

  Up to 2 cycles(each cycle 28 days)

• The measurement of the area under the plasma concentration-time versus time curve(AUC)

  Up to 2 cycles(each cycle 28 days)

• The measurement of elimination half life (T1/2)

  Up to 2 cycles(each cycle 28 days)

• The measurement of time of maximum plasma concentration (Tmax)

  Up to 2 cycles(each cycle 28 days)

• The Measurement of mean retention time (MRT)

  Up to 2 cycles(each cycle 28 days)

Study Arms (1)

SHR7390

EXPERIMENTAL

60 subjects with advanced solid tumors were received single and then multiple oral doses of SHR7390(2 cycles,each cycle 28days).

Drug: SHR7390

Interventions

SHR7390 DRUG

SHR7390 is provided as white, film-coated,immediate release tablets containing SHR7390 at dosage strengths of 0.125 mg and 0.5 mg. Multiple tablets of SHR7390 will be administered daily to achieve targeted doses of SHR7390: 0.25 mg-4 mg. Tablets will be orally administered with 240 ml water, once daily, 2 hours after a meal.

Also known as: MEK inhibitor

SHR7390

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be included to participate in this study each patient must:
• years of age, both women and men;
• invalid the standard treatment or non standard and effective treatment in patients with advanced solid tumors diagnosed by pathology;
• the Eastern Cooperative Oncology Group （ECOG） General status (performance status, PS) of 0-1;
• the expected lifetime ≥ 3 months;
• organ function you must meet the following requirements:
• Adequate bone marrow reserve: including neutrophil absolute count,platelets and hemoglobin;
• Liver: serum albumin ≥ 3.0 g/dl; bilirubin, Alanine aminotransferase（ALT）and aspartate aminotransferase（AST）≤ 1.5 x upper limit of normal value (ULN),if there is liver metastasis, the ALT or AST
• x upper limit of normal value (ULN);
• Kidneys: creatinine clearance ≥ 50 mL/min (Cockcroft-Gault of the standard formula）；
• Heart: left ventricular ejection fraction ≥ 50%; normal Electrocardiograph (ECG) and corrected QT interval（QTc）;
• The damage of the patients caused by other treatments has been restored;
• A agreement to use a highly effective, non-hormonal form of contraception is required for women of childbearing potential and men with partners of childbearing potential, who were not sterilized surgically, for duration of the study treatment and after the last dose of study treatment; For female patients of child bearing potential,who was not sterilized surgically,the serum human chorionic gonadotropin （HCG） pregnancy test must be the negative
• Written informed consent is provided by signing the informed consent form.

You may not qualify if:

• Subjects who meet any of the criteria listed below will not be eligible for participation in this study. A patient will not be eligible for study participation if:
• Previous treatment with other protein kinase MEK inhibitors;
• Use of other investigational anti-cancer drugs or the termination of the investigational drugs within the last four weeks;
• Currently or possibly receiving other cancer therapy during the study period;
• Presence of a factor that influences the oral drug (such as inability to swallow) or presence of active gastrointestinal disease or other conditions that will interfere significantly with the absorption, distribution, metabolism, or excretion of drug;
• History of retinal vascular occlusion （RVO） or central serous retinopathy;
• Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein thrombosis or central serous retinopathy;
• Intraocular pressure\>21mmHg as measured by tonography or glaucoma;
• Tumor metastases of central nervous system or leptomeningeal metastases. primary malignancy of the central nervous system;
• Evidence of severe or uncontrolled systemic diseases (e.g. unstable or uncompensated respiratory, hepatic, renal or cardiac diseases);
• History of acute coronary syndromes (including unstable angina);
• Presence of arrhythmia, myocardial ischemia with drug intervention. III-IV stage heart failure as defined by the New York Heart Association (NYHA) functional classification system.
• Medical treatment for an acute phase of infection;
• hepatitis B virus（HBV) or hepatitis C virus (HCV) infection stage with abnormal liver function;
• History of immunodeficiency, or other acquired and congenital immunodeficiency disease;

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

The Cancer Center,Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Interventions

MEK inhibitor I

Study Officials

• RuiHua Xu, MD, PhD

  The Cancer Center,Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

RuiHua Xu, MD, PhD

CONTACT

86-20-8734-3008; xurh@sysucc.org.cn

Yi Liu, PhD

CONTACT

86-21-6045-3192; liuy@shhrp.com

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: October 7, 2016
• First Posted: November 18, 2016
• Study Start: November 1, 2016
• Primary Completion: April 1, 2019
• Study Completion: July 1, 2019
• Last Updated: January 15, 2019

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)