Inclusion Criteria:

• At least 18 years of age at the time of study randomization.
• Histologically confirmed metastatic and/or unresectable GIST.
• Measurable disease on CT or MRI as defined by RECIST.
• Documented radiographic progression or intolerance to imatinib and sunitinib.
• Clinical failure of the most recent prior therapy for GIST. Note: There is no limit to the number of prior therapies a patient may have received.
• Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1.
• Hemoglobin ≥ 8.0 g/dL (80 g/L).
• Absolute Neutrophil Count ≥ 1500/µL (1.5 x 109/L).
• Platelets ≥ 100,000 /µL (100 x 109/L).
• ALT and AST ≤ 2.5 x upper limit of normal (ULN), or ≤ 5.0 x ULN if considered secondary to liver metastases.
• Alkaline phosphatase ≤ 2.5 x ULN, or ≤ 5.0 x ULN if considered secondary to liver metastases.
• Serum bilirubin ≤ 1.5 x ULN.
• PT and PTT ≤ 1.5 x ULN unless the patient is receiving warfarin. If the patient is receiving warfarin, the INR must be within therapeutic range.
• Serum creatinine ≤ 1.5 x ULN.

Exclusion Criteria:

• Previous administration of other known heat shock protein 90 (Hsp90) inhibitors.
• Surgery, radiotherapy, or lesion ablative procedure to the only area of measurable disease.
• Initiation or discontinuation of concurrent medication that is a potent CYP3A inhibitor less than 2 weeks prior to administration of IPI-504 or placebo.
• History of any of the following within the last 6 months: cardiac disease such as acute coronary syndrome or unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, cirrhotic liver disease, cerebrovascular accident, or any other significant co-morbid condition or disease which, in the judgment of the investigator, would place the patient at undue risk or interfere with the study.
• Grade 3 or 4 hemorrhagic event within the last 6 months.
• Known human immunodeficiency virus positivity.
• Sinus bradycardia (resting heart rate < 50 bpm) secondary to intrinsic conduction system disease.
• QTcF ≥ 470 milliseconds, or previous history of clinically significant QTc prolongation while taking other medications.
• History of prior malignancies within the past 3 years other than non-melanomatous skin cancers that have been controlled, prostate cancer that has been treated and has not recurred, non-muscle-invasive bladder cancer, and carcinoma in situ of the cervix.
• Active or recent history (within 3 months) of keratitis or keratoconjunctivitis confirmed by ophthalmology or optometry exam.
• Presence of Left Bundle Branch Block, Right Bundle Branch Block plus left anterior hemiblock, bifascicular block, or 3rd degree heart block. This does not include patients with a history of these events with adequate control by pacemaker.
• Known CNS metastases.
• Women who are pregnant or lactating.