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) [ Time Frame: At 6 and 12 weeks then every 9 weeks thereafter, expected 1 year ] [ Designated as safety issue: No ]Measured from time of randomization until objective tumor progression or death.
- Response Rate (RR) [ Time Frame: Measured by repeat scans at 6 and 12 weeks then every 9 weeks thereafter, projected 1 year ] [ Designated as safety issue: No ]Defined as the proportion of complete and partial responses assessed per RECIST v1.1.
- Overall survival (OS) [ Time Frame: Measured by repeat scans at 6 and 12 weeks then every 9 weeks thereafter, projected 1 year ] [ Designated as safety issue: No ]Measured from the time of randomization until death from any cause.
- Frequency of Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Days 1, 8 and 15 (Cycles 1 - 2) plus ≥30 days of finishing treatment or study discontinuation, projected 1 year ] [ Designated as safety issue: Yes ]Assessed according to NCI CTCAE v4.0
|Study Start Date:||December 2011|
|Study Completion Date:||February 2015|
|Primary Completion Date:||February 2015 (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 partial response (PR) rate was 3% and stable disease (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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01404650
|United States, Connecticut|
|Yale School of Medicine|
|New Haven, Connecticut, United States, 06520|
|United States, Florida|
|Florida Cancer Specialists-South|
|Ft. Myers, Florida, United States, 33916|
|Florida Hospital Cancer Institute|
|Orlando, Florida, United States, 32804|
|Woodlands Medical Center|
|Pensacola, Florida, United States, 32503|
|Florida Cancer Specialists-North|
|St. Petersburg, Florida, United States, 33705|
|United States, Missouri|
|Research Medical Center|
|Kansas City, Missouri, United States, 64132|
|United States, Nebraska|
|Nebraska Methodist Hospital|
|Omaha, Nebraska, United States, 68114|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|Study Chair:||Johanna Bendell, MD||SCRI Development Innovations, LLC|