Trametinib in Treating Patients With Advanced Cancer With or Without Hepatic Dysfunction

Official Title

A Phase I Trial of Single Agent Trametinib (GSK1120212) in Advanced Cancer Patients With Hepatic Dysfunction

Summary:

This phase I trial studies the side effects and best dose of trametinib in treating patients with cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) with or without liver (hepatic) dysfunction. Trametinib may stop the growth of tumour cells by blocking proteins needed for cell growth. When these proteins are blocked, the growth of cancer cells may be stopped and the cancer cells will then die. Hepatic dysfunction is frequently found in patients with advanced cancer and usually prevents patients from receiving standard treatments or from participating in clinical trials. Patients may also need dose adjustments or absorb drugs differently. Trametinib may be a better treatment for patients with advanced cancers and hepatic dysfunction.

Trial Description

Primary Outcome:

• Maximum tolerated dose of trametinib
• Dose-limiting toxicity assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
• Pharmacokinetic profile of trametinib

Secondary Outcome:

• Non-dose-limiting toxicities associated with the administration of trametinib
• Objective response to treatment assessed using the Response Evaluation Criteria in Solid Tumours criteria 1.1
• Predictive biomarkers for individual cancer patients utilizing genomic sequencing technologies

PRIMARY OBJECTIVES:
I. To provide appropriate dosing recommendations for patients with varying degree of hepatic dysfunction receiving trametinib (mild, moderate and severe). II. To establish the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of trametinib in advanced cancer patients with varying degrees of hepatic dysfunction. III. To characterize the pharmacokinetic (PK) profile of trametinib in advanced cancer patients with varying degrees of hepatic dysfunction. SECONDARY OBJECTIVES:
I. To document the non-DLTs associated with the administration of trametinib in patients with varying degrees of hepatic dysfunction. II. To document any antitumour activity associated with trametinib treatment of patients enrolled on this study. III. To explore and characterize predictive biomarkers for individual cancer patients utilizing genomic sequencing technologies. OUTLINE:

This is a dose-escalation study. Patients receive trametinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks.

View this trial on ClinicalTrials.gov