study evaluating ipi-504 in patients with gastrointestinal stromal tumors (gist) following failure of at least imatinib and sunitinib

Conditions: Gastrointestinal Stromal Tumors

Summary: ipi-504-06 is a phase 3, randomized, double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of ipi-504 as compared to placebo in patients with metastatic and/or unresectable gist following failure of at least imatinib and sunitinib. approximately 195 patients will be randomized using a 2:1 ratio to receive either ipi-504 (n=130) or placebo (n=65). upon unblinding, patients receiving either ipi-504 or placebo may receive ipi-504 in the open-label portion of the study if defined inclusion criteria are met. early and frequent imaging timepoints (weeks 2, 5, 8, 14 and every 6 weeks thereafter) are incorporated into this study to capture progression events and limit patient exposure to ineffective agents.


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.

Keywords: gist metastatic and/or unresectable gastrointestinal stromal