Metastatic and/or unresectable gastro-intestinal stromal tumors in patients following failure of treatment with at least imatinib and sunitinib. MedDRA version: 9.1 Level: LLT Classification code 10062427 Term: Gastrointestinal stromal tumor
Conditions
Interventions
Product Name: Retaspimycin hydrochloride
Product Code: IPI-504
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: Retaspimycin hydrochloride
Current Sponsor code: I
Sponsors
Infinity Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following: 1. At least 18 years of age at the time of study randomization. 2. Histologically confirmed metastatic and/or unresectable GIST. 3. Measurable disease on computed tomography (CT) or magnetic resonance imaging (MRI) as defined by RECIST with at least one measurable lesion. 4. Documented radiographic progression or intolerance to imatinib and sunitinib. 5. 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 (e.g., patients may have received treatment with nilotinib, other TKIs, or chemotherapy in addition to imatinib or sunitinib). 6. Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1. 7. Administration of the last dose of imatinib or nilotinib =1 week, any other TKI = 2 weeks, chemotherapy, radiotherapy, surgery, ablative therapy, biologic therapy (e.g., antibodies, vaccines), or any other investigational therapy ? 4 weeks prior to randomization. 8. Resolution of all toxic effects of imatinib, sunitinib, other TKIs, surgery, radiotherapy, chemotherapy, lesion ablative therapy, or investigational therapy to baseline or Grade 1 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. 9. Patients must have acceptable baseline normal organ and marrow function as defined below: •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). •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x upper limit of normal (ULN), or = 3.0 x ULN if considered secondary to liver metastases. •Alkaline phosphatase = 2.5 x ULN, or = 3.0 x ULN if considered secondary to liver metastases. •Serum bilirubin = 1.5 x ULN. •Prothrombin time (PT) and partial thromboplastin time (PTT) = 1.5 x ULN unless the patient is receiving warfarin. If the patient is receiving warfarin, the international normalized ratio (INR) must be within therapeutic range. •Serum creatinine = 1.5 x ULN. •Albumin = 3.0 g/dL. 10.Women of reproductive potential (defined as being less than 1 year post-menopausal) must have a negative serum or urine ß human chorionic gonadotropin (ßHCG) pregnancy test; and men and women of reproductive potential must agree to practice an effective method of avoiding pregnancy while receiving study drug and for 30 days after the final dose of study drug. Effective contraception includes use of oral contraceptives with an additional barrier method, double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, and total abstinence. 11.Written informed consent obtained from the patient prior to receipt of any study medication or beginning study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients must have none of the following: 1. Previous administration of 17-allylamino-17-demethoxygeldanamycin (17-AAG), 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), or other known heat shock protein 90 (Hsp90) inhibitors. 2. Surgery, radiotherapy, or lesion ablative procedure to the only area of measurable disease. 3. Use of a medication or food that is a clinically relevant CYP3A inhibitor or inducer within 2 weeks prior to administration of IPI-504 or placebo. A list of clinically relevant CYP3A inhibitors and inducers is found in Appendix 2. Patients who are on a stable dose of a drug that is not listed in Appendix 2 but is known to alter CYP3A activity for > 2 weeks are eligible to enroll. 4. Patients with a 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 (e.g., psychiatric or other conditions). 5. Grade 3 or 4 hemorrhagic event within the last 6 months. 6. Known human immunodeficiency virus positivity. 7. Sinus bradycardia (resting heart rate < 50 bpm) secondary to intrinsic conduction system disease. Patients with sinus bradycardia secondary to pharmacologic therapy may enroll if withdrawal of the therapy results in normalization of the resting heart rate to within normal limits. 8. Baseline QT corrected using Fridericia’s correction method (QTcF) = 470 milliseconds (msec), or previous history of clinically significant QTc prolongation while taking other medications. 9. 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. 10. Active or recent history (within 3 months) of keratitis or keratoconjunctivitis confirmed by ophthalmology or optometry exam. 11. 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. 12. Patients with known central nervous system (CNS) metastases. Patients with symptoms indicative of CNS metastases must have a head CT or brain MRI at screening. 13. Women who are pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare the progression free survival (PFS) following administration of IPI-504 plus best supportive care versus placebo plus best supportive care in patients with metastatic and/or unresectable gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib.;Secondary Objective: 1. Compare the disease control rate (DCR) in both arms of the study. 2. Compare the time to progression (TTP) in both arms of the study. 3. Compare the overall survival (OS) in both arms of the study. 4. Evaluate the safety and tolerability of IPI-504 in this patient population.;Primary end point(s): The primary assessment of antitumor activity is progression free survival (PFS). PFS is defined as the time from randomization to the first documentation of disease progression or death due to any cause, whichever occurs first. Disease progression is defined as radiographic progression by Response Evaluation Criteria in Solid Tumors (RECIST). | — |
Countries
Czech Republic, Denmark, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed