Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor

Inclusion Criteria

• •1. Pts with histologically-confirmed metastatic or unresectable GIST who have progressed on, are intolerant of, or are not a candidate for imatinib and sunitinib therapy. Pts must not have received prior treatment with Hsp90 inhibitors.
• •2. Must have an ECOG Performance Status of 0-1.
• •3. Must have a life expectancy of ≥3 mos.
• •4. Must have at least one unidimensional measurable lesion definable by MRI or CT scan. Disease must be measurable per RECIST v1.1.
• •5. Must have normal serum phosphorus and magnesium ≥ the lower limit of normal prior to trial entry.
• •6. Normal bone marrow function defined as: ANC ≥1500/μL Hgb ≥9 g/dL Plt ≥100,000/L
• •7. Adequate hepatic function defined as: AST or ALT and ALP must be 2.5 x ULN, or ≤5 x ULN in pts with liver mets Total bilirubin ≤1.5 x the institutional ULN
• •8. Renal function defined as: Serum creatinine ≤1.5 x ULN or 24-hour CrCl 50 mL/min
• •9. Women of childbearing potential (WOCP) must have a negative serum or urine pregnancy test performed ≤7 days prior to start of treatment.
• •10. Must be accessible for treatment and follow-up.
• •11. Must be able to understand the investigational nature of this study and give written informed consent prior to study entry
• •4. Treatment with therapeutic doses of coumadin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted).
• •5. Impaired cardiac function with any one of the following: History (or family history) of prolong QT syndrome. Mean QTc ≥450 msec on baseline ECG. History of clinically manifested IHD ≤6 mos prior to study start. History of heart failure or any history of left ventricular (LV) dysfunction (LVEF ≤45%) by MUGA or ECHO. Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block, right bundle branch block with left anterior hemiblock. ST segment elevation or depression \>1 mm, or 2nd (Mobitz II) or 3rd degree AV block. History or presence of A-Fib, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes. Other clinically significant heart disease. Clinically significant resting bradycardia (\<50 beats per minute). Currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes and cannot be switched to an alternative drug or discontinued prior to commencing AUY922. Obligate use of a cardiac pacemaker.
• •6. Known diagnosis of HIV, Hep C virus, or acute or chronic Hep B infection.
• •7. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• •8. Women who are pregnant or lactating.
• •9. Any condition that would prevent patient comprehension of the nature of, and risk associated with, the study, and the inability to comply with study and/or follow-up procedures.
• •10. Other malignancies ≤3 years, with the exception of adequately treated basal or squamous cell carcinomas of the skin, carcinoma in situ of the cervix, or localized prostate cancer with a current PSA of \<1.0 mg/dL on 2 successive evaluations, at least 3 mos apart, with the most recent evaluation no more than 4 wks prior to entry.