A Phase I Trial of 17-Allylaminogeldanamycin (17-AAG) in Solid Tumor and Lymphoma Patients

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), administered at 2 different dosing schedules, in patients with unresectable solid tumors.
• Determine the pharmacokinetics of this drug in these patients.
• Assess the effect of this drug on heat shock protein chaperone complex components and client proteins in lymphoma tissue obtained pre- and post-treatment in patients with relapsed lymphoma.
• Determine any response to this drug in these patients.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 treatment groups.

• Group I: Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Group II: Patients receive 17-AAG IV over 1 hour on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 solid tumor patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.