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.
Gastrointestinal stromal tumors (GIST) are common sarcomas that arise in the gastrointestinal tract. Sunitinib (Pfizer) and imatinib (Novartis) are FDA-approved for treatment of patients with GIST. However, patients with advanced or refractory GIST who are resistant to these agents eventually experience disease progression or death. Heat shock protein-90 (Hsp90) is a substance found in various malignancies that encourages tumor cells to grow and survive. As an inhibitor of Hsp90, AUY922 may decrease growth of tumor cells that were resistant to prior therapies. This study investigates AUY922 monotherapy as treatment for patients who either progressed on, or were resistant to, imatinib and sunitinib.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
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.
Yale School of Medicine
New Haven, Connecticut, United States
Florida Cancer Specialists-South
Fort Myers, Florida, United States
Florida Hospital Cancer Institute
Orlando, Florida, United States
Woodlands Medical Center
Pensacola, Florida, United States
Progression-free Survival (PFS)
Measured from time of randomization until objective tumor progression or death; assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Progressive disease (PD) defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest (nadir) sum since the treatment started, or the appearance of one or more new lesions.
Time frame: At 6 and 12 weeks then every 9 weeks thereafter until progression or intolerable toxicity, up to 4 years.
Response Rate (RR)
Defined as the proportion of complete and partial responses, assessed per RECIST v1.1. Complete response (CR) defined as a disappearance of all lesions; partial response (PR) defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking the baseline sum LD as reference. Stable Disease (SD) defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for progressive disease, taking as reference the smallest (nadir) sum LD since start of treatment.
Time frame: At 6 and 12 weeks then every 9 weeks thereafter until progressive disease or intolerable toxicity, for up to 4 years.
Overall Survival (OS)
Evidence of survival was obtained by clinic visit or telephone contact from the time of first dose until death from any cause.
Time frame: Every 3 months until patient death or lost to follow-up, for up to 4 years.
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Worst toxicity grades per patient were tabulated for select adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 4.0
Time frame: Days 1, 8 and 15 of each 21-day cycle plus 30 days after treatment discontinuation.
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Florida Cancer Specialists-North
St. Petersburg, Florida, United States
Research Medical Center
Kansas City, Missouri, United States
Nebraska Methodist Hospital
Omaha, Nebraska, United States
Tennessee Oncology
Nashville, Tennessee, United States