RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: This phase I trial is studying the side effects and best dose of a geldanamycin analogue in treating patients with advanced cancer.
OBJECTIVES: * Determine the maximum tolerated dose for a geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin (AAG), in patients with advanced malignancies. * Determine the toxic effects and dose-limiting toxicity of AAG in this patient population. * Determine the safe dose of AAG for a Phase II study. * Measure the pharmacokinetic and pharmacodynamic profiles of AAG in these patients. * Assess time to tumor progression and any antitumor activity in patients treated with AAG. OUTLINE: This is a dose-escalation study. Patients receive a geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin (AAG), IV over 15-30 minutes every week. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Patients are followed at 4 weeks. PROJECTED ACCRUAL: Approximately 20-40 patients will be accrued for this study.
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Royal Marsden NHS Foundation Trust - London
London, England, United Kingdom
Recommended phase II dose of 17-allylamino-17-demethoxygeldanamycin (17-AAG) at 4 weeks
Heat shock protein 90 (HSP90) client protein and co-chaperone changes during first course of treatment
Pharmacokinetic profile of 17-AAG during the first course of treatment
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