Sorafenib and Erlotinib in Treating Patients With Metastatic or Unresectable Solid Tumors
RATIONALE: Sorafenib and erlotinib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib and erlotinib in treating patients with metastatic or unresectable solid tumors.
Unspecified Adult Solid Tumor, Protocol Specific
Drug: erlotinib hydrochloride
Drug: sorafenib tosylate
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of BAY 43-9006 (Sorafenib) in Combination With OSI-774 (Erlotinib; Tarceva) in Advanced Solid Tumors|
- Maximum tolerated dose and recommended phase II dose [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Pharmacodynamic outcomes [ Time Frame: Pre study and cycle 1 ] [ Designated as safety issue: No ]
- Pharmacokinetic outcomes [ Time Frame: Pre-study, cycle 1 and cycle 2 ] [ Designated as safety issue: No ]
- Antitumor activity [ Time Frame: Every 8 wks ] [ Designated as safety issue: No ]
- Correlation of EGFR, AKT, ERK and VEGFR with antitumor activity [ Time Frame: If responses or prolonged stable disease are observed ] [ Designated as safety issue: No ]
- EGFR activating mutations, gene amplification status, EGFR intron 1 polymorphism if responses or prolonged disease stabilization are seen [ Time Frame: If responses or prolonged stable disease are observed ] [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Experimental: OSI-774 erlotinib) and Bay 43-9006 (Sorafenib)
Sorafenib administered alone for a 1-week run-in period, and then both drugs e given together continuously, with every 28 days considered as a cycle. Three dose levels assessed.
|Drug: erlotinib hydrochloride Drug: sorafenib tosylate|
- Determine the maximum tolerated dose and recommended phase II dose of sorafenib and erlotinib in patients with metastatic or unresectable solid tumors.
- Determine the optimal biologically effective dose of this regimen that will lead to hypophosphorylation of epidermal growth factor receptor (EGFR), ERK, Akt, and vascular endothelial growth factor receptor (VEGFR), and inhibition of angiogenesis and apoptosis with tolerable toxicity in these patients.
- Correlate the pharmacokinetic profiles of this regimen with toxicity and biological activity in these patients.
- Determine, preliminarily, the antitumor activity of this regimen in these patients.
- Correlate phosphorylation status of EGFR, ERK, Akt, and VEGFR with antitumor activity of this regimen in these patients.
OUTLINE: This is a multicenter, open label, non-randomized, dose-escalation study.
Patients receive oral sorafenib alone once or twice daily on days -6 to 0*. Patients then receive oral sorafenib once or twice daily and oral erlotinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
NOTE: *Not considered part of course 1; considered a "run-in" period only.
Cohorts of 3-6 patients receive escalating doses of sorafenib and erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD.
After completion of study treatment, patients are followed at 4 weeks and then at least annually thereafter.
PROJECTED ACCRUAL: A total of 16-28 patients will be accrued for this study within 5-14 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00126620
|Margaret and Charles Juravinski Cancer Centre|
|Hamilton, Ontario, Canada, L8V 5C2|
|Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Study Chair:||Lillian L. Siu, MD, FRCPC||Princess Margaret Hospital, Canada|