Trametinib in Treating Patients With Advanced Cancer With or Without Hepatic Dysfunction
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|ClinicalTrials.gov Identifier: NCT02070549|
Recruitment Status : Recruiting
First Posted : February 25, 2014
Last Update Posted : August 4, 2021
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm Metastatic Malignant Neoplasm in the Liver Metastatic Malignant Solid Neoplasm Unresectable Solid Neoplasm||Drug: Trametinib||Phase 1|
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.
I. To document the non-DLTs associated with the administration of trametinib in patients with varying degrees of hepatic dysfunction.
II. To document any antitumor 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. Cycles 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||68 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Single Agent Trametinib (GSK1120212) in Advanced Cancer Patients With Hepatic Dysfunction|
|Actual Study Start Date :||February 12, 2014|
|Estimated Primary Completion Date :||July 31, 2022|
|Estimated Study Completion Date :||July 31, 2022|
Experimental: Treatment (trametinib)
Patients receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Maximum tolerated dose of trametinib [ Time Frame: 28 days ]Dose escalation and determination of the maximum tolerated dose will be carried out separately for each cohort or stratum. Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a sub-analysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to one or both study treatments.
- Dose-limiting toxicity [ Time Frame: 28 days ]Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 beginning April 1, 2018). Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a sub-analysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to one or both study treatments.
- Pharmacokinetic profile of trametinib [ Time Frame: Baseline and 0.5, 1, 2, 3, 4, 6, 10, and 24 hours on days 15 and 16 of cycle 1 ]Attempts to model associations between pharmacokinetic data with toxicity profiles will be performed primarily using descriptive statistics; however, logistic regression may be used if warranted.
- Non-dose-limiting toxicities associated with the administration of trametinib [ Time Frame: Up to 4 weeks post treatment ]Will document in patients with varying degrees of hepatic dysfunction.
- Objective response to treatment [ Time Frame: Up to 4 weeks post treatment ]Will be assessed using the Response Evaluation Criteria in Solid Tumors criteria 1.1. Summary statistics, such as the mean, median, counts and proportion, will be used to describe patients' clinical characteristics.
- Predictive biomarkers for individual cancer patients [ Time Frame: Up to 4 weeks post treatment ]Will be assessed by utilizing genomic sequencing technologies. Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Potential predictors include clinical predictors and molecular correlates. Descriptive statistics and plotting of data will also be used to better understand potential relationships.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02070549
|United States, California|
|University of California Davis Comprehensive Cancer Center||Suspended|
|Sacramento, California, United States, 95817|
|United States, Florida|
|Moffitt Cancer Center||Suspended|
|Tampa, Florida, United States, 33612|
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center||Active, not recruiting|
|Chicago, Illinois, United States, 60637|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute||Active, not recruiting|
|Detroit, Michigan, United States, 48201|
|United States, Missouri|
|Washington University School of Medicine||Suspended|
|Saint Louis, Missouri, United States, 63110|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey||Active, not recruiting|
|New Brunswick, New Jersey, United States, 08903|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center||Suspended|
|Columbus, Ohio, United States, 43210|
|United States, Texas|
|M D Anderson Cancer Center||Suspended|
|Houston, Texas, United States, 77030|
|Canada, British Columbia|
|BCCA-Vancouver Cancer Centre||Active, not recruiting|
|Vancouver, British Columbia, Canada, V5Z 4E6|
|Juravinski Cancer Centre at Hamilton Health Sciences||Suspended|
|Hamilton, Ontario, Canada, L8V 5C2|
|University Health Network-Princess Margaret Hospital||Recruiting|
|Toronto, Ontario, Canada, M5G 2M9|
|Contact: Site Public Contact 416-946-4501 email@example.com|
|Principal Investigator: Lillian L. Siu|
|Principal Investigator:||Lillian L Siu||University Health Network Princess Margaret Cancer Center LAO|