E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastrointestinal stromal tumour (GIST) |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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 |
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E.4 | Principal 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) < 1.5 x 109 /L • Platelet count < 100 x 10 9 /L (without transfusion within 2 weeks of study day 1) • Hemoglobin < 9 g/dL • Serum creatinine > 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response as defined using modified RECIST criteria |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |