Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor
Condition: Gastrointestinal Stromal Tumor
MeSH terms: Gastrointestinal Stromal Tumors
Intervention: AUY922
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GIST; Refractory; Gastrointestinal; Stromal; Tumor

Summary:

      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.
    

Eligibility criteria:

        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

        Exclusion Criteria:

          1. Currently receiving or have received cancer therapies ≤21 days of initiating study
             therapy. For pts receiving small molecule targeted therapy, study treatment may begin
             ≥21 days after last dose or ≥5 half lives of previous treatment, whichever is shorter.
             The patient must have recovered from or come to a new chronic stable baseline from all
             treatment-related toxicities.

          2. Use of any non-approved or investigational agent ≤30 days of administration of the
             first dose of study drug. Pts may not receive any other investigational or anti-cancer
             treatments while participating in this study.

          3. Uncontrolled brain mets. Pts with treated brain mets (resection or radiotherapy) are
             eligible if brain mets have responded to treatment as documented by CT or MRI scan
             obtained at ≥2 wks after completion of RT, neurologic symptoms are absent, and
             steroids have been discontinued.

          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.