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

A Phase 1, Open-label, Dose-escalation Study of the Safety of SNX-5422 Mesylate 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 Overview

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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
  • Georgia
    • Augusta, Georgia, United States, 30901
      • Georgia Regents University Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt-Ingram Cancer Center

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:

• Males or non-pregnant, non-breastfeeding females 18 years-of-age or older with histologically confirmed non-Hodgkins lymphoma, without known or clinically suspected CNS involvement, that is refractory to available therapy or for which there is no available therapy.
• No more than 4 prior lines of systemic anti-cancer therapy and no prior bone marrow transplant or stem cell transplant within 12 months of dosing, and no prior allogeneic transplant.
• Karnofsky performance score ≥60
• Life expectancy of at least 3 months.
• Adequate baseline laboratory assessments

Exclusion Criteria:

• Currently receiving anticancer therapy or have received anticancer therapy within the past 28 days or 5 half-lives of the anticancer therapy
• The need for treatment with medications with clinically-relevant metabolism by the cytochrome P450 (CYP) 3A4 isoenzyme within 3 hours before or after administration of SNX-5422
• At increased risk for developing prolonged QT interval, including hypokalemia or hypomagnesemia, unless corrected to within normal limits prior to first dose of SNX-• Chronic diarrhea.
• Gastrointestinal diseases or conditions that could affect drug absorption, including gastric bypass.
• Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
• History of documented adrenal dysfunction not due to malignancy.
• Seropositive for human immunodeficiency virus (HIV) or hepatitis C virus (HCV).
• History of chronic liver disease

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 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	Drug: SNX-5422; Capsule dosed every other day for 21 days out of 28 day cycle. 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 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	First 28 day cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events as a measure of tolerability	Frequency and severity of AEs, changes in vital signs, ECG, physical examination and clinical chemistry, hematology and urinalysis	Day 28 of each cycle
Tumor progression	Hematological disease assessment of all known sites of disease using the appropriate hematological malignancy response criteria compared to baseline	Completion of every two 28 day cycles

Collaborators and Investigators

• Sponsor: Esanex Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: July 4, 2012
• First Submitted That Met QC Criteria: July 6, 2012
• First Posted (Estimate): July 9, 2012

Study Record Updates

• Last Update Posted (Actual): April 26, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Hsp90; Hematological Malignancy
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: SNX-5422-CLN1-005