PK Trial of Sorafenib & Erlotinib in Patients With Refractory Solid Tumors
Two cohorts of patients will be enrolled: Cohort A will consist of patients who are current smokers, and Cohort B will consist of patients who are current nonsmokers. There will be 24 patients enrolled in each cohort. Nonsmokers are patients who have not consumed tobacco or nicotine-containing products for 1 year before the start of the study. Patients classified as current smokers must have smoked a minimum of 10 cigarettes per day for ≥1 year. Patients who have smoked 1-9 cigarettes per day for ≥1 year or more than 10 cigarettes per day for <1 year will not be eligible for this study.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pharmacokinetic Trial of Sorafenib and Erlotinib in Patients With Refractory Solid Tumors|
- To determine the pharmacokinetics (PK) of erlotinib when administered in combination with sorafenib on a continuous schedule in Refractory Solid Tumors in patients who are smokers and in patients who are nonsmokers. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- To evaluate safety of this combination in patients with Refractory Solid Tumors. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2008|
|Estimated Study Completion Date:||December 2012|
|Estimated Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
Patients will receive erlotinib 150 mg once daily by mouth and sorafenib 400 mg twice daily by mouth. The study will begin with a 2-week run-in period (which will begin on Day 14 of the study, and continue through Day 1 of the study), in which erlotinib will be dosed alone at 150 mg once daily. Patients will continue taking erlotinib as a single agent at 150 mg once daily through Day 1. After the 2-week run-in period, patients will receive continuous dosing of both agents (erlotinib 150 mg once daily and sorafenib 400 mg twice daily) in cycles of 28 days each. Toxicity will be assessed every cycle (every 4 weeks) for all patients. Because this is not an efficacy study, restaging tumor measurements will be at the discretion of the physician every 8 weeks during treatment. Patients with objective response or stable disease will continue therapy; patients with disease progression or unacceptable toxicity will be discontinued from the study.
150 mg once daily by mouthDrug: Sorafenib
400 mg twice daily by mouth
Compared with supportive care alone, erlotinib has been associated with improved overall survival in patients with Refractory Solid Tumors; however, this absolute benefit is limited for the majority of patients. Incorporating other biologic agents into the second- or third-line treatment setting may prove to be a successful strategy in improving treatment efficacy (which has been recently demonstrated in several tumor types). Additionally, recent data suggest that smoking may influence the pharmacokinetic (PK) profile of erlotinib by increasing the metabolic clearance. Data suggest that the geometric mean erlotinib AUC(0-inf) and C(24h) are significantly decreased in smokers compared with nonsmokers (Hamilton et al. 2006). For this reason, this trial will enroll separate cohorts of patients who are current smokers and patients who are nonsmokers. Nonsmokers are patients who have not consumed tobacco or nicotine-containing products for 1 year before the start of the study. Patients classified as current smokers must have smoked a minimum of 10 cigarettes per day for ≥1 year.