A Phase I and Pharmacologic Study of 17-(Allylamino)-17-Demethoxygeldanamycin (AAG, NSC 330507) in Adult Patients With Solid Tumors
I. To determine the maximum tolerated dose of geldanamycin analogue (AAG) in patients with
advanced solid tumors.
II. To determine the toxic effects of this drug in this patient population. III. To
determine the biochemical and molecular effects of this drug in normal and accessible tumor
tissue in these patients.
IV. To determine the pharmacokinetics of this drug in these patients. V. To assess any
antitumor activity of this drug in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive geldanamycin analogue (AAG) IV over 1-6 hours once daily on days 1, 4, 15,
and 18. Courses repeat every 4 weeks 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 2
of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional
10 patients are treated at the MTD.
Patients are followed every 6 weeks.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of tanespimycin
DLT are defined as any greater than or equal to grade 3 non-hematologic toxicity (except for alopecia of any grade, grade 3 nausea or vomiting during less than maximal antiemetic therapy, and grade 3 fever in the absence of neutropenia and infection), any grade 4 hematologic toxicity (except for anemia of any grade), or the inability to resume treatment by day 42 (longer than two week delay) because of drug related toxicity.
University of Nebraska
United States: Food and Drug Administration
|University of Nebraska Medical Center||Omaha, Nebraska 68198-3330|