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

Cancer Clinical Trial

Official title:

A Phase 1, Open-label, Dose-escalation Study of the Safety of SNX-5422 Mesylate in Subjects With Refractory Hematological Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01635712
• Other study ID #: SNX-5422-CLN1-005
• Status: Completed
• Phase: Phase 1
• First received: July 4, 2012
• Last updated: April 25, 2017
• Start date: February 2014
• Est. completion date: February 2017

Study information

• Verified date: April 2017
• Source: Esanex Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hsp90 is a chemical in the body that is involved int he promotion of cancer. SNX-5422 is an experimental drug that blocks Hsp90.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: February 2017
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• SNX-5422
Capsule dosed every other day for 21 days out of 28 day cycle. Dose escalation based on safety

Locations

Country	Name	City	State
United States	Georgia Regents University Cancer Center	Augusta	Georgia
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Esanex Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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