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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Cancer

Intervention / Treatment
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* Drug: SNX-5422


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SNX-5422<br>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<br>* Tablets dose every other day; dose escalation based on safety<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hsp90, Solid tumor malignancy