Cancer
Conditions
Keywords
Solid tumor malignancy, Hsp90
Brief summary
Hsp90 is a chemical in the body that is involved in promotion of cancer. SNX-5422 is an experimental drug that blocks Hsp90. It is being evaluated for safety in patients with cancer.
Detailed description
Correlation has been observed between Hsp90 client protein level changes and functional effects in cells in in vitro studies of SNX-5422, 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. 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 drug, monitoring of the QTc interval at appropriate time points, and a conservative dose-escalation scheme.
Interventions
DRUGSNX-5422
Tablets dose every other day; dose escalation based on safety
Sponsors
Esanex Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \>18 years old histologically confirmed solid tumor malignancy refractory to available therapy or for which no therapy is available adequate organ function
Exclusion criteria
* CNS malignancy significant GI disease at risk for prolonged QT interval
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with dose limiting toxicities | First 28 day cycle | Number of patients with dose limiting toxicities defined as Grade 3 or higher on the CTCAE version 4.03 clearly related to disease progression in each dose cohort during the first cycle of study drug administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic profiles of parent drug and metabolite | Day 1 and Day 21 first cycle | Assessment of standard pharmacokinetic parameters including area under the plasma-concentration time curve, volume of distribution, clearance elimination half life |
| Number of patients with adverse events as a measure of tolerability | Day 28 of each cycle | Frequency and severity of AEs, changes in vital signs (including self-reported pain), ECG, physical examination, and clinical laboratory parameters (clinical chemistry, hematology, and urinalysis). |
Outcome results
None listed