Primary Outcome Measures:
- Tumor response rate (complete and partial response) [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Progression-free survival [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Toxicity as assessed by CTCAE version 3.0 [ Designated as safety issue: Yes ]
- Relationship of tumor response rate with DNA isolation and sequencing of BRAF and ras mutation analysis [ Designated as safety issue: No ]
- Levels of BRAF and ras mutation in the tumor [ Designated as safety issue: No ]
- Protein levels of p-ERK/ERKERK [ Designated as safety issue: No ]
- Pharmacokinetic profile of AZD6244 [ Designated as safety issue: No ]
OBJECTIVES:
Primary
- To examine the tumor response rate in patients with recurrent low-grade serous ovarian cancer treated with AZD6244.
- To examine the acute toxicity of this drug during the first course of treatment.
- To examine DNA isolation with sequencing of BRAF and ras mutation analysis and to explore their relationship with tumor response in patients treated with this drug.
Secondary
- To examine the toxicity of this drug using the 21 major categories of the CTCAE version 3.0.
- To examine the dose and number of courses of AZD6244 given.
- To estimate the progression-free survival and overall survival of patients treated with this drug.
- To examine protein levels of p-ERK/ERKERK and explore their relationship with tumor response in patients treated with this drug.
- To define the pharmacokinetic profile of AZD6244.
OUTLINE: This is a multicenter study.
Patients receive oral AZD6244 twice a day on days 1-28 in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection periodically for correlative and pharmacokinetic studies and to analyze AZD6244 peak concentrations and the corresponding peak time values. Previously collected archived tumor tissue samples are obtained to determine protein levels of p-ERK/ERKERK, DNA isolation and sequencing of BRAF and ras mutation analysis by immunohistochemistry (IHC).
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year for 5 years.