Gastrointestinal stromal tumour (GIST)
Conditions
Interventions
Product Name: AMG 706
Product Code: AMG 706
Pharmaceutical Form: Tablet
Current Sponsor code: AMG 706
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Product N
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Disease related • Men and women = 18 years old with histologically confirmed GIST that express CD117+ • Subject must have documented treatment with imatinib mesylate at least 600 mg daily for at least 8 weeks • Presence of at least one measurable (per modified RECIST) and progressing tumor lesion that has not previously been treated with radiotherapy or embolization, and that can be evaluated by contrast enhanced CT or MRI • Subject must have documented radiographic disease progression during previous treatment with imatinib mesylate. Prestudy disease progression (as defined by modified RECIST) is defined as an increase of = 20% in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD, or the appearance of a new lesion. The period of time covered by the 2 CT scans which demonstrate disease progression may include treatment with 400 mg, but must include at least 8 weeks of treatment with at least 600 mg imatinib mesylate, and include radiographic evidence of continued tumor growth = 10% sum LD during treatment with 600 mg. • Subject must be off imatinib mesylate for at least 7 days before study day 1 (imatinib mesylate washout) • Karnofsky performance status of = 60. Ethical • Before any study-specific procedure is performed, signed and dated written informed consent must be obtained 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: Disease Related • Symptomatic central nervous system tumor involvement • Prior malignancy (other than GIST, in situ cervical cancer, or basal cell cancer of the skin), unless treated with curative intent and without evidence of disease for = 3 years • Myocardial infarction, or unstable or uncontrolled disease or condition related to or impacting cardiac function (eg, unstable angina, congestive heart failure [New York Heart Association > class II]) within 1 year of study day 1 • Subjects with uncontrolled hypertension as defined by systolic BP >145 mm Hg or diastolic BP > 85 mm Hg are excluded (see section on BP measurement during screening phase). Patients on anti-hypertensive medication must meet these parameters on a stable anti-hypertensive medication regimen • History of arterial thrombosis or deep vein thrombosis (including plumonary embolus) within 1 year of study day 1 • Recent major surgical procedure (within 28 days of study day 1) Laboratory • Absolute neutrophil count (ANC) 2.0 mg/dL • Urine protein quantitative value of > 1+ on dipstick, = 30 mg/dL in urinalysis, or > 500 mg in 24-hour urine collection • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x upper limits of normal (ULN), or AST or ALT > 5.0 x ULN if secondary to liver metastasis; • Alkaline phosphatase > 2.5 x ULN, or alkaline phosphatase > 5 x ULN in the presence of bone or liver metastasis • Total bilirubin > 2 x ULN Medications • Previous exposure to AMG 706 or other tyrosine kinase inhibitors of c-kit (except imatinib mesylate) or VEGF (vascular endothelial growth factor) type (eg, SU5416, SU6668, SU11248, PTK787) • Coumarin-type anticoagulants (including warfarin) > 2 mg/day must not be administered within 7 days before study day 1 • Currently or previously treated with rifampin or phenobarbitol (within 14 days of study day 1) or ketoconazole, itraconazole, erythromycin, clarithromycin, nefazodone, cyclosporine, tacrolimus, and any HIV protease inhibitor (within 7 days of study day 1) • Concurrent therapy with St. John’s Wort General • Other investigational procedures are excluded. • Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s). • Subject of child-bearing potential is evidently pregnant (eg, positive HCG test) or is breast feeding. • Subject is not using adequate contraceptive precautions. • Subject has known sensitivity to any of the products to be administered during dosing. • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the treatment effect of AMG 706 on the objective response rate as assessed by modified RECIST criteria in subjects with advanced GISTs who developed progressive disease or relapsed per modified RECIST while on imatinib mesylate.;Secondary Objective: To assess the treatment effect of AMG 706 on duration of response, progression-free survival, time to disease progression, time to response, and overall survival. To explore patient-reported outcomes, performance status, palliative response, and opioid analgesic use with AMG 706 treatment. To explore the utility of using 18FDG-PET scan at week 8 and target tumor size and density changes at week 8 (from computed tomography [CT]) scan for the prediction of tumor response. To assess pharmacokinetic profiles of AMG 706 and explore pharmacokinetic/pharmacodynamic relationships To assess the safety profile of AMG 706 in subjects with GIST.;Primary end point(s): Objective response as defined using modified RECIST criteria | — |
Countries
Germany, Italy, United Kingdom
Outcome results
None listed