A Phase I Dose Escalation, Single Center, Open-Label Study of AUY922 Administered IV on a Once-Weekly Schedule in Adult Patients 75 Years of Age or Older With Advanced Solid Malignancies
I. The primary objective is to determine the maximally tolerated dose (MTD) of AUY922 (Hsp90
inhibitor AUY922) as a single agent when administered intravenously (IV) on a once-weekly
schedule to adult patients 75 years of age or older with advanced solid tumors whose disease
has progressed despite standard therapy or for whom no standard therapy exists.
I. To characterize the safety and tolerability of treatment with AUY922. II. To characterize
the pharmacokinetic profiles of AUY922, including the parent drug and any potential
III. To determine the efficacy of AUY922 in elderly patients with measurable disease.
IV. To evaluate of effect of geriatric-focused assessment of comorbidity and functional
status on the toxicity and response to AUY922.
V. To assess the ethical constraints to enrollment of elderly patients in phase I trials.
I. Determine the effect of therapy with AUY922 on the number of circulating tumor cells
II. To assess changes HSP70 induction as a measure of pharmacodynamic effect in pre- and
post-AUY922 samples in peripheral blood mononuclear cell (PBMCs) to explore age-related
differences in HSP90 inhibition by AUY922 compared with the previous phase I trial.
III. To assess changes in cellular response markers of apoptosis in pre- and post-AUY922
dosing in peripheral blood including measurement of M30 and M65 to explore age-related
differences in pharmacodynamics compared to patients enrolled in the previous phase I trial.
IV. To determine associations between pharmacokinetic (PK) and pharmacodynamic (PD)
V. To determine the relationship between geriatric-focused assessment of comorbidity and
functional ability and toxicity and response.
OUTLINE: This is a dose-escalation study.
Patients receive Hsp90 inhibitor AUY922 IV over 1 hour on days 1, 8, 15, and 22. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 28 days.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of Hsp90 inhibitor AUY922
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as clinically relevant, and occurs < 28 days following the first dose of AUY922. Toxicity will be measured by CTCAE criteria (Version 4.02). The MTD will be determined using a standard design.
at 28 days
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
United States: Food and Drug Administration
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center||Cleveland, Ohio 44195|