Safety and Pharmacology Study of SNX-5422 in Subjects With Refractory Solid Tumor Malignancies

Phase 1

Completed

• Conditions: Cancer
• Interventions: Drug: SNX-5422

• Registration Number: NCT01611623
• Lead Sponsor: Esanex Inc.

Brief Summary

Hsp90 is a chemical in the body that is involved in promotion of cancer. SNX-5422 is an experimental drug that blocks Hsp90. It is being evaluated for safety in patients with cancer.

Detailed Description

Correlation has been observed between Hsp90 client protein level changes and functional effects in cells in in vitro studies of SNX-5422, supporting inhibition of Hsp90 as the mechanism of action for this compound. SNX-5422 has demonstrated significant antitumor activity in mouse xenograft models of human tumors, including breast (BT474, MX-1), colon (HT29), prostate (PC3), and melanoma (A375) with multiple oral dosing regimens. This study will employ critical risk management features including the use of the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03, which provides a scale for consistently grading the severity of AEs, toxicity criteria analyses for dose escalation, frequent laboratory and clinical observations, correlation of AEs with plasma concentrations of drug, monitoring of the QTc interval at appropriate time points, and a conservative dose-escalation scheme.

Study Timeline

• Study Start: 2012-05
• Study First Submitted: 2012-05-25
• Study First Submitted QC: 2012-05-31
• Study First Posted: 2012-06-05
• Primary Completion: 2012-11
• Status Verified: 2013-03
• Study Completion: 2013-03
• Last Update Submitted: 2013-03-29
• Last Update Posted: 2013-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

• >18 years old histologically confirmed solid tumor malignancy refractory to available therapy or for which no therapy is available adequate organ function

Exclusion Criteria

• CNS malignancy significant GI disease at risk for prolonged QT interval

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SNX-5422	SNX-5422	Open label administration of SNX-5422 tablets every other day for 21 days on a 28 day cycle. Dose escalation based on safety outcomes

Primary Outcome Measures

Name	Time	Method
Number of patients with dose limiting toxicities	First 28 day cycle	Number of patients with dose limiting toxicities defined as Grade 3 or higher on the CTCAE version 4.03 clearly related to disease progression in each dose cohort during the first cycle of study drug administration

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic profiles of parent drug and metabolite	Day 1 and Day 21 first cycle	Assessment of standard pharmacokinetic parameters including area under the plasma-concentration time curve, volume of distribution, clearance elimination half life
Number of patients with adverse events as a measure of tolerability	Day 28 of each cycle	Frequency and severity of AEs, changes in vital signs (including self-reported pain), ECG, physical examination, and clinical laboratory parameters (clinical chemistry, hematology, and urinalysis).