Cediranib Maleate and Selumetinib Sulfate in Treating Patients With Solid Malignancies

Description

PRIMARY OBJECTIVES:

I. To determine the maximally tolerated dose of cediranib maleate (AZD2171 [cediranib]) in combination with selumetinib sulfate (AZD6244 hydrogen sulfate).

II. To describe the toxicity profile associated with AZD2171 (cediranib) in combination with AZD6244 hydrogen sulfate.

III. To describe the tumor responses and identify any activity of this AZD2171 (cediranib) in combination with AZD6244 hydrogen sulfate.

IV. To explore, through correlative studies, the effect of AZD2171 (cediranib) with or without AZD6244 hydrogen sulfate on serum markers of apoptosis.

V. To assess the pharmacokinetic interaction of AZD2171 (cediranib) in combination with AZD6244 hydrogen sulfate.

VI. To study the association of clinical (toxicity and/or tumor response or activity) with the pharmacologic (pharmacokinetic/pharmacodynamic) parameters, and/or biologic (correlative laboratory study) results.

OUTLINE: This is a dose-escalation study followed by a dose-expansion cohort study.

Patients receive cediranib maleate orally (PO) once daily (QD) and selumetinib sulfate PO QD or twice daily (BID) on days 1-28 (days 8-28 of cycle 1). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cycles may be extended to 12 weeks after 1 year of study treatment.

After completion of study therapy, patients are followed up at 3 months.