A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study Evaluating the Efficacy and Safety of IPI-504 in Patients With Metastatic and/or Unresectable GIST Following Failure of at Least Imatinib and Sunitinib
- 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
- 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.
- Previous administration of other known heat shock protein 90 (Hsp90) inhibitors.
- Surgery, radiotherapy, or lesion ablative procedure to the only area of measurable
- 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
- 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
- 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.