A Phase I Dose Escalation Study of the PKC Inhibitor, Aurothiomalate (ATM) in Patients With Advanced Non-Small Cell Lung Cancer

OBJECTIVES:

• To determine the maximum tolerated dose of gold sodium thiomalate in patients with advanced non-small cell lung cancer.
• To describe the toxicities associated with this treatment.
• To describe any preliminary evidence of biologic activity.
• To further assess the correlation between PKCι expression and the antitumor effects of gold sodium thiomalate.
• To study the association of clinical (toxicity and/or tumor response or activity) with pharmacokinetic/pharmacodynamic parameters.
• To describe anti-proliferative activity of gold sodium thiomalate through 3-deoxy-3-[^18F]-fluorothymidine positron emission tomography imaging.

OUTLINE: This is a dose-escalation study of gold sodium thiomalate.

Patients receive gold sodium thiomalate intramuscularly on days 1, 8, 15 and 22. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive gold sodium thiomalate once every 4 weeks until a total cumulative dose of 1 gram is delivered.

Blood samples are collected at baseline and prior to therapy in weeks 3, 5, 7, 9, and 11. Samples are analyzed by mass spectometry for pharmacokinetics. Paraffin-embedded tumor tissue samples are analyzed for PKC_l expression and antitumor activity. Antiproliferative effects of gold sodium thiomalate are analyzed by 3-deoxy-3-[^18F]-fluorothymidine positron emission tomography imaging.