Hsp90 Inhibitor AUY922 in Treating Older Patients With Advanced Solid Malignancies

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title: 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

Status Terminated

Clinical Trial Summary

This phase I trial studies the side effects and best dose of Hsp90 inhibitor AUY922 in treating older patients with advanced solid malignancies. Hsp90 inhibitor AUY922 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Clinical Trial Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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 metabolites.

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.

TERTIARY OBJECTIVES:

I. Determine the effect of therapy with AUY922 on the number of circulating tumor cells (CTC).

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) parameters.

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. ;

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Adult Solid Tumor, Protocol Specific

• NCT number: NCT01602627
• Study type: Interventional
• Source: Case Comprehensive Cancer Center
• Status: Terminated
• Phase: Phase 1
• Start date: September 2011
• Completion date: February 2012