Safety and Pharmacology Study of SNX-5422 in Subjects With Refractory Hematological Malignancies
Hsp90 is a chemical in the body that is involved int he promotion of cancer. SNX-5422 is an experimental drug that blocks Hsp90.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Open-label, Dose-escalation Study of the Safety of SNX-5422 Mesylate in Subjects With Refractory Hematological Malignancies|
- Number of patients with dose limiting toxicities [ Time Frame: First 28 day cycle ] [ Designated as safety issue: Yes ]Number of patients with dose-limiting toxicities defined as AEs or laboratory abnormalities of Common Terminology Criteria for Adverse Events [CTCAE] version 4.03 ≥ Grade 3 that are not clearly related to disease progression
- Number of patients with adverse events as a measure of tolerability [ Time Frame: Day 28 of each cycle ] [ Designated as safety issue: Yes ]Frequency and severity of AEs, changes in vital signs, ECG, physical examination and clinical chemistry, hematology and urinalysis
- Tumor progression [ Time Frame: Completion of every two 28 day cycles ] [ Designated as safety issue: No ]Hematological disease assessment of all known sites of disease using the appropriate hematological malignancy response criteria compared to baseline
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||December 2012|
|Estimated Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Open label administration of SNX-5422 capsules every other day (QOD) for 21 days on a 28 day cycle. Dose escalation will be based on safety outcomes defined as 1 or less dose limiting toxicities during the first 28 day cycle at any dose level
Capsule dosed every other day fro 21 days out of 28 day cycle. Dose escalation based on safety
SNX-5422 is a prodrug for SNX-2112. Correlation has been observed between Hsp90 client protein level changes and functional effects in cells in in vitro studies of SNX-2112, 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. Pharmacokinetic (PK) studies in mice, rats, and dogs have shown high bioavailability of SNX-2112 following oral administration of SNX 5422. In mouse xenograft studies, SNX-2112 was selectively retained in tumor tissue compared with other tissues. 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 SNX-5422 and SNX-2112, monitoring of the QTc interval at appropriate time points, and a conservative dose-escalation scheme.