A Phase I Study of 17-AAG in Relapsed/Refractory Pediatric Patients With Solid Tumors or Leukemia
I. To estimate the maximum tolerated dose (MTD) and recommended phase II dose of 17-AAG
administered as a 60 or 120-minute intravenous infusion on days 1, 4, 8, and 11, of a 21-day
course, to children with refractory solid tumors or relapsed leukemia.
II. To define and describe the toxicities of 17-AAG administered on this schedule.
III. To characterize the pharmacokinetics of 17-AAG in children with refractory cancer.
I. To preliminarily define the antitumor activity of 17-AAG within the confines of a phase I
II. To assess the biologic activity of 17-AAG. III. To examine the role of CYP3A5
polymorphisms in the pharmacologic and clinical phenotypes observed following administration
of 17-AAG to children, within the confines of a phase 1 study.
OUTLINE: This is a dose-escalation, multicenter study.
Patients with solid tumors receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over
60-120 minutes on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 17 courses
in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 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. Once the MTD is determined, up to 6 additional patients
with leukemia receive 17-AAG at the MTD as above. If these 6 patients tolerate this regimen,
another 6 leukemia patients receive 17-AAG IV over 60 minutes on days 1, 4, 8, 11, 15, and
Treatment repeats every 28 days for 17 courses in the absence of disease progression or
unacceptable toxicity. Patients are followed at 30 days.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD defined as the maximum dose at which fewer than one-third of patients experience DLT
COG Phase I Consortium
United States: Food and Drug Administration
|COG Phase I Consortium||Arcadia, California 91006-3776|