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

A Phase 1, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of SNX-5422 in Subjects With Refractory Solid Tumor Malignancies or Non-Hodgkin's Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: SNX-5422

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: SNX-5422; Tablets dose every other day; dose escalation based on safety

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with dose limiting toxicities	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	First 28 day cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profiles of parent drug and metabolite	Assessment of standard pharmacokinetic parameters including area under the plasma-concentration time curve, volume of distribution, clearance elimination half life	Day 1 and Day 21 first cycle
Number of patients with adverse events as a measure of tolerability	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).	Day 28 of each cycle

Collaborators and Investigators

• Sponsor: Esanex Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: May 25, 2012
• First Submitted That Met QC Criteria: May 31, 2012
• First Posted (Estimate): June 5, 2012

Study Record Updates

• Last Update Posted (Estimate): April 2, 2013
• Last Update Submitted That Met QC Criteria: March 29, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Hsp90; Solid tumor malignancy
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SNX-5422-CLN1-004