Selumetinib in Treating Patients With Locally Advanced or Metastatic Liver Cancer
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Other: pharmacological study
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of AZD6244 in Advanced or Metastatic Hepatocellular Carcinoma|
- Number of Participants With Radiographic Objective Response (OR) [ Time Frame: 33 weeks ] [ Designated as safety issue: No ]
To ascertain the objective response rate (Complete Response + Partial Response [CR+PR]) of patients with the single-agent AZD6244. Our study utilized Response Evaluation Criteria in Solid Tumors (RECIST) to evaluate response.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- Median Progression Free Survival (PFS) [ Time Frame: 33 weeks ] [ Designated as safety issue: No ]Progression free survival has been defined as time from the start of treatment to disease progression or death as a result of any cause.
- Median Overall Survival (OS) [ Time Frame: 33 weeks ] [ Designated as safety issue: No ]Overall survival has been defined as time from the start of treatment to death as a result of any cause.
|Study Start Date:||November 2007|
|Study Completion Date:||June 2012|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor therapy)
Patients receive a single dose of selumetinib on day 1 and undergo blood collection for PK sampling pre-dose (within 30 min of dosing), 15 and 30 minutes and 1, 2, 4, 8, 12, 24 and 48 hours post-dose. Beginning 48 hours after the initial dose and continuing until day 21, patients receive oral selumetinib twice daily. Patients also undergo blood collection for PK sampling on day 15 of course 1. In all subsequent courses, patients receive selumetinib on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Other Names:Other: pharmacological study
Other Name: pharmacological studies
I. To ascertain the objective response rate (complete response and partial response) in patients with locally advanced or metastatic hepatocellular carcinoma treated with AZD6244 (selumetinib).
I. To assess the safety and tolerability of AZD6244 when administered to patients with hepatocellular carcinoma and mild (Child's A to compensated Child's B) liver dysfunction.
II. To describe the pharmacokinetics (PK) of AZD6244 in this patient population and compare in exploratory fashion to the established PK profile in patients with normal hepatic function.
III. To estimate the time to event functions of progression, progression-free survival (PFS), (and PFS associated with treatment), and overall survival.
IV. To explore, preliminarily, the possible correlations between baseline mitogen-activated protein kinase (MEK) activation (i.e., presence of phospho-MEK) and radiographic response or time to progression.
V. To investigate the effects of AZD6244 on MEK kinase activity in peripheral blood mononuclear cells from patients treated with this drug.
Patients receive a single dose of selumetinib on day 1 and undergo blood collection for pharmacokinetic (PK) sampling pre-dose (within 30 min of dosing), 15 and 30 minutes and 1, 2, 4, 8, 12, 24 and 48 hours post-dose. Beginning 48 hours after the initial dose and continuing until day 21, patients receive oral selumetinib twice daily. Patients also undergo blood collection for PK sampling on day 15 of course 1. In all subsequent courses, patients receive selumetinib on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Selumetinib blood concentrations are quantified by high performance liquid chromatography. Patients also undergo tumor biopsy by CT or ultrasound guidance at baseline and on day 8. Peripheral blood mononuclear cells and tumor tissue are evaluated for mitogen-activated protein kinase baseline activity and post-treatment activity.
After completion of study treatment, patients are followed periodically for up to 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00604721
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|United States, Georgia|
|Atlanta, Georgia, United States, 30322|
|United States, North Carolina|
|University of North Carolina|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Ohio|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|United States, Virginia|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Bert O'Neil||H. Lee Moffitt Cancer Center and Research Institute|