An Open-Labeled Non-Randomized Phase I Study of 17-N-allylamino-17-demethoxy Geldanamycin (17AAG) Administered With Irinotecan (CPT-11) in Patients With Advanced Solid Tumors
I. To determine the maximum tolerated dose (MTD) of combined 17AAG and irinotecan given
weekly for two weeks in a 21-day cycle that can be used for future phase II studies.
I. To explore the effects of the combination on the expression of Hsp90 client proteins in
peripheral mononuclear cells and tumor tissues. Tumor biopsies will be performed before and
after 17AAG treatment in 12 patients at the MTD ("Expanded Cohort") only.
II. To investigate the clinical pharmacokinetics of intravenous 17AAG, irinotecan, and their
metabolites, in this combination.
III. To obtain preliminary data on the therapeutic activity of 17AAG in combination with
irinotecan in patients with advanced solid tumors.
IV. To obtain preliminary result in the relationship between tumor response and p53-status.
OUTLINE: This is an open-label, non-randomized, dose-escalation study.
Patients receive irinotecan IV over 30 minutes followed by
17-N-allylamino-17-demethoxygeldanamycin (17-AAG)* IV over 2 hours on days 1 and 8.
Treatment repeats every 21 days for at least 2 courses in the absence of disease progression
or unacceptable toxicity. Patients achieving stable or improved disease after course 2 may
receive additional courses of treatment.
NOTE: *17-AAG is administered on days 2 and 8 during course 2 for patients treated at
non-maximum tolerated doses (MTD) (dose-escalation portion) and on day 8 only during course
1 for patients treated at the MTD (expanded cohort).Cohorts of 3-6 patients receive
escalating doses of 17-AAG and irinotecan until the MTD is determined. The MTD is defined as
the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting
toxicity. An additional 12 patients are treated at the MTD.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose determined by dose-limiting toxicities
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|