Clinical trial NCT01635712: Safety and Pharmacology Study of SNX-5422 in Subjects With Refractory Hematological Malignancies
Official title: A Phase 1, Open-label, Dose-escalation Study of the Safety of SNX-5422 Mesylate in Subjects With Refractory Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: Hematological Malignancy
Hsp90
Lead sponsor: Esanex Inc.
Sponsor class: INDUSTRY
First posted: 2012-07-09
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of patients with dose limiting toxicities
timeFrame: First 28 day cycle
Secondary outcomes:
measure: Number of patients with adverse events as a measure of tolerability
timeFrame: Day 28 of each cycle
measure: Tumor progression
timeFrame: Completion of every two 28 day cycles
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Augusta
country: United States
facility: Georgia Regents University Cancer Center
state: Georgia
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
References: