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

NCT ID: NCT01635712

Last Updated: 2017-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2017-02-28

Brief 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.

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.

Conditions

Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

SNX-5422

Intervention Type: DRUG

Capsule dosed every other day for 21 days out of 28 day cycle. Dose escalation based on safety

Interventions

SNX-5422

Capsule dosed every other day for 21 days out of 28 day cycle. Dose escalation based on safety

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Esanex Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

Georgia Regents University Cancer Center

Augusta, Georgia, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

SNX-5422-CLN1-005

Identifier Type: -

Identifier Source: org_study_id