A Phase I Trial Of 17-Allylaminogeldanamycin (17-AAG) And PS341 In Advanced Malignancies
I. Determine the dose-limiting toxicity and maximum tolerated dose of
17-N-allylamino-17-demethoxygeldanamycin (17-AAG) (tanespimycin) and bortezomib in patients
with advanced solid tumors or lymphomas (Accrual for Lymphoma Patients Closed as of
II. Determine changes in biomarkers (e.g., HSP70, client proteins, and ubiquitination of
proteins) in peripheral blood mononuclear cells and tumor specimens from patients with
advanced solid tumors or lymphomas (Accrual for Lymphoma Patients Closed as of 11/27/09)
treated with this regimen.
III. Determine responses in patients treated with this regimen. IV. Determine the toxic
effects of this regimen in these patients.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive tanespimycin intravenously (IV) over 1-2 hours and bortezomib IV over 3-5
seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of
tanespimycin and bortezomib until the maximum tolerated dose (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. Once the MTD is determined, at least 12 additional patients are
treated as above* at the MTD.
NOTE: *Bortezomib is not administered on day 1 of course 1 only. Patients are followed at 3
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of tanespimycin in combination with bortezomib in the treatment of solid tumors
Defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of the solid tumor patients (at least 2 of a maximum of 6 new patients).
At 3 weeks
United States: Food and Drug Administration
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