Clinical trial NCT00688766 (phase 3, status: terminated)
Conditions: gastrointestinal stromal tumors
ICD codes: C49.A0, C49.A1, C49.A2, C49.A5, C49.A3, C49.A4, C49.A9
Drugs: retaspimycin hydrochloride (ipi-504), placebo
SMILES: CO[C@H]1C[C@H](C)CC2=C(NCC=C)C(O)=CC(NC(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@H]1O)=C2O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    based on independent data monitoring committee (idmc) recommendation.
  
Eligibility criteria:

        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.