Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor
This is a multicenter, non-randomized, single agent, Phase II study of AUY922 in patients with refractory Gastrointestinal Stromal Tumor (GIST). The primary endpoint of this study is to determine progression-free survival (PFS) for patients with GIST receiving AUY922 intravenously (IV) on Days 1, 8, and 15 of a 21-day treatment cycle with restaging at 6 and 12 weeks and then every 9 weeks thereafter. Patients may continue treatment until evidence of disease progression.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor|
- Progression-free survival (PFS) will be analyzed using Kaplan-Meier methods. [ Time Frame: 18 months ] [ Designated as safety issue: No ]Historical controls in the refractory setting currently suggest a median PFS of 6 weeks. We hypothesize under the AUY922 regimen that the median PFS will be improved to at least 12 weeks.
- response rate (RR) in patients by repeat scans [ Time Frame: 18 months ] [ Designated as safety issue: No ]Confirmation of response by repeat scans Every 6 wks (Cycles 1-4) then every 9 wks.
- Overall survival (OS) of patients will be analyzed using Kaplan-Meier methods. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- Determine the Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]The analyses of safety will be based on the frequency of Adverse Events (AEs) and their severity for patients who received at least one dose of study treatment. Worst toxicity grades per patient will be tabulated for select AEs and laboratory measurements by using NCI CTCAE criteria v4.0.
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||September 2013|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
AUY922: 70 mg/m2 IV over 60 minutes on Days 1, 8, and 15 of each cycle. Treatment cycles will be repeated every 21 days. Patients will be evaluated for response at 6 and 12 weeks and then every 9 weeks (i.e., every 3 cycles) thereafter. Patients may continue treatment until evidence of disease progression.
Preclinical data have shown that Hsp90 inhibition can lead to decrease in tumor growth of GIST tumors that are both imatinib-sensitive and imatinib-resistant (Bauer 2006). A recently reported phase I trial evaluated Hsp90 inhibitor IPI-504 for the treatment of patients with GIST refractory to tyrosine kinase inhibitors (Wagner 2008). In this study, 100% of patients had been previously exposed to imatinib and 93% to sunitinib. For 36 patients treated on this trial, the PR rate was 3% and SD was 67%, with a median PFS of 12 weeks. This is significantly improved over a placebo median PFS of 6 weeks for patients treated with sunitinib versus placebo who were refractory for imatinib (Demetri 2006).
|Contact: Johanna Bendell, MDfirstname.lastname@example.org|
|Contact: Trials Infoemail@example.com|
|United States, Florida|
|Florida Cancer Specialists||Recruiting|
|Ft. Myers, Florida, United States, 33916|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|Study Chair:||Johanna Bendell, MD||Sarah Cannon Research Institute|