TREATMENT OF PATIENTS WITH GASTROINTESTINAL STROMAL TUMORS (GIST) MedDRA version: 8.1 Level: LLT Classification code 10051066 Term: Gastrointestinal stromal tumour
Conditions
Interventions
Trade Name: Sutent
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: sunitinib (as malate)
CAS Number: 341031-54-7
Current Sponsor code: SU011248
Other descriptive name: PHA-290940AD
Concentrati
Sponsors
Pfizer Inc., East 42nd Street, New York, NY 10017
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histopathologically proven diagnosis of malignant GIST that is not amenable to surgery, radiation, or combined modality therapy with curative intent. 2. Evidence of unidimensionally measurable disease (ie, > or equal 1 malignant tumor mass that may be accurately measured in at least 1 dimension > or equal 20 mm with conventional radiographic techniques or magnetic resonance imaging [MRI], or if spiral computerized tomography [CT] scan, twice the reconstruction interval used [lesion size > or equal 10-16 mm depending on interval]). Tumor evaluation by positron emission tomography (PET) scan or by ultrasound may not substitute for CT or MRI scans. Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions, and disease documented by indirect evidence only (eg, by laboratory tests such as alkaline phosphatase) are not considered measurable. 3. Currently being treated with imatinib mesylate. Treatment with imatinib must be continued until randomization. 4. Must have experienced failure of prior treatment with imatinib mesylate 400 mg per day defined by progression of disease according to RECIST criteria during treatment. Radiographic evidence of disease progression on imatinib mesylate must be confirmed by the Investigator prior to enrollment in the study. 5. Male or female, 18 years of age or older. 6. ECOG performance status 0 or 1. 7. Resolution of all toxic effects of any prior imatinib mesylate therapy, surgical procedures, radiotherapy, or cryotherapy to NCI CTCAE (Version 3.0) Grade or equal 3.0 g/dL • Absolute neutrophil count (ANC) > or equal 1500/microliter • Platelets > or equal 100,000/microliter • Hemoglobin > or equal 9.0 g/dL • Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Current treatment with any chemotherapy, chemoembolization therapy, immunotherapy, or investigational anticancer agent other than imatinib mesylate. 2. Treatment of subjects with imatinib mesylate resistant disease with surgery, radiotherapy, and/or cryotherapy that affected all areas of measurable disease where progression on imatinib mesylate therapy had been demonstrated. 3. Having previously discontinued use of imatinib prior to randomization. 4. Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri. 5. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event. 6. Treatment with potent CYP3A4 inhibitors and inducers within 7 and 12 days, respectively, prior to study drug administration. Potent CYP3A4 inhibitors and inducers will not be allowed as concomitant medications during the study. 7. Current treatment with therapeutic doses of anticoagulant (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). 8. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). 9. Pre existing thyroid abnormality of thyroid function that cannot be maintained in the normal range with medication. 10. Ongoing cardiac dysrhythmias of NCI CTCAE Grade > or equal 2, atrial fibrillation of any Grade, or prolongation of the QTc interval to >450 msec for males or >470 msec for females. 11. Left ventricular ejection fraction (LVEF) < or equal 50% as measured by either multigated acquisition (MUGA) scan or echocardiogram (ECHO). 12. Evidence of neurological signs/symptoms secondary to brain metastases, spinal cord compression, or new evidence of brain or leptomeningeal disease. 13. Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS) related illness. 14. Pregnancy or breastfeeding. Subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) within the 7 days prior to enrollment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. 15. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the progression-free survival (PFS) associated with sunitinib (37.5 mg daily) with that associated with imatinib 800 mg daily in subjects whose disease progressed on imatinib 400 mg daily. ;Secondary Objective: •To compare the objective response rates (OR) between the two regimens •To assess time to tumor response (TTR) between the two regimens in responders •To compare duration of response (DR) between the two regimens in responders •To compare time to treatment failure (TTF) between the two regimens •To compare overall survival between the two regimens •To assess pain relief / pain progression in the two regimens •To assess patient-reported outcomes (PROs) •To evaluate safety and tolerability of the two drug regimens ;Primary end point(s): The primary endpoint of the main study is progression free survival (PFS). Progression free survival is defined as the time from randomization to first progression of disease (PD) or death for any reason in the absence of documented PD. Observation time for calculating PFS will be censored on the date of the last tumor assessment on study for subjects who do not have objective tumor progression and who do not die while on study. Subjects lacking an evaluation of tumor response after randomization will have their PFS time censored on the date of randomization with a duration of 1 day. Subjects who start a new anti cancer therapy without documented PD prior to start of this therapy will be censored at the date of the last tumor assessment prior to the start of the new therapy. | — |
Countries
France, Germany, Italy, Spain, United Kingdom
Outcome results
None listed