Safety and Efficacy of SNX-5422 in Human Epidermal Growth Factor Receptor 2 (HER2) Positive Cancers
Hsp90 is a chemical in the body that is involved in the promotion of cancer. SNX-5422 is an experimental drug that blocks Hsp90
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Single Arm, Phase 1/2 Study of SNX-5422 in Subjects With Selected HER2 Positive Cancers.|
- Objective Response Rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]The effect of SNX-5422 on tumor progression. Objective tumor responses (complete remissions plus partial remissions) and clinical benefit rate (complete remissions plus partial remissions plus stable disease ≥ 6 months) will be listed by subject. Tumor measurements made using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.Progression free survival and overall survival (time frame: every 3 months until 24 months after the last patient has been enrolled) will be listed by subject.
- Number of patients with adverse events [ Time Frame: Day 28 of each cycle ] [ Designated as safety issue: Yes ]Number and percentage of patients experiencing treatment emergent adverse events described by relationship to treatment and severity.
- Changes in vital signs, physical examination or clinical laboratory from baseline [ Time Frame: Day 28 of each cycle ] [ Designated as safety issue: Yes ]Descriptive summaries of vital signs, physical examination and quantitative clinical laboratory changes will be presented by treatment received and study visit. Laboratory toxicities will be graded by severity using common terminology criteria for adverse events (CTCAE) Version 4.03. Frequency and percentage of subjects experiencing clinically relevant toxicities will be summarized by treatment received. Summaries may be repeated by treatment cycle.
- Ophthalmologic changes from baseline [ Time Frame: Day 28 of every 3 cycles ] [ Designated as safety issue: Yes ]Ophthalmologic assessments will be presented by cohort, study visit and dose. Number of subjects experiencing clinically relevant changes from baseline in any of these examinations will be presented using descriptive summary
|Study Start Date:||April 2013|
|Estimated Study Completion Date:||May 2015|
|Estimated Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Open-label administration of SNX-5422 capsules to total 100 mg/m2 every other day for 21 days (total = 11 doses), out of a 28-day treatment cycle. Subjects will continue treatment on a 28-day cycle at the discretion of the principal investigator based on safety.
Capsule(s) dosed every other day for 21 days (total = 11 doses), out of a 28-day treatment cycle.
Heat shock protein 90 (Hsp90) chaperone proteins stabilize well over 200 different known client proteins helping them to fold correctly as they take up their rightful positions in the cell. Hsp90 has a special fondness for oncoproteins whose structures shift according to functional state. Among Hsp90's clients, a surprising number are well recognized targets in oncology, including human epidermal growth factor receptor 2 (HER2). SNX-5422 is a pro-drug of SNX-2112, a potent, highly selective, small-molecule inhibitor of the molecular chaperone heat shock protein 90 (Hsp90). Treatment of HER2-positive cell lines such as BT-474 with the Hsp90 inhibitor SNX-2112 results in cellular degradation, decreased levels of phospho-AKT/cyclin D1, and increased apoptosis. Furthermore, treatment with SNX-5542 caused tumor regression, including remission in a HER2-overexpressing breast cancer xenograft model. SNX-5422 has demonstrated significant antitumor activity in mouse xenograft models of various human malignancies, including breast (BT474, MX-1), lung (H1975, H1650, EBC-1), colon (HT29), prostate (PC3), and melanoma (A375) with multiple oral dosing regimens.
|Contact: Eric Orlemans, PhDemail@example.com|
|United States, Arizona|
|Scottsdale, Arizona, United States, 85258|
|Contact: Joyce Schaffer, RN MSN 877-273-3713 firstname.lastname@example.org|
|Principal Investigator: Jasgit Sachdev, MD|
|United States, District of Columbia|
|Georgetown University Medical Center||Recruiting|
|Washington, District of Columbia, United States, 20007|
|Contact: Giuseppe Giaccone, MD 202-687-5791 email@example.com|
|Principal Investigator: Giuseppe Giaccone, MD|
|United States, New Jersey|
|Hackensack University Medical Center||Recruiting|
|Hackensack, New Jersey, United States, 07601|
|Contact: Martin Gutierrez, MD 551-996-5900 mgutierrez@hackensackUMC.org|
|Principal Investigator: Martin Gutierrez, MD|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Michelle Maziarz 646-888-4425 firstname.lastname@example.org|
|Contact: Martin H Voss, MD 646-422-4631 email@example.com|
|Principal Investigator: Martin H Voss, MD|