Study of AMG 706 in Subjects With Advanced Gastrointestinal Stromal Tumors (GISTs)

Study Overview
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Brief Summary
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This study will determine the safety and effectiveness of AMG 706 in patients with advanced GIST.

Detailed Description
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Expanded Access: Amgen provides expanded access for this clinical trial. Contact the Amgen Call Center (866-572-6436) for more information.

Official Title
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An Open Label Study of AMG 706 in Subjects With Advanced Gastrointestinal Stromal Tumors (GISTs) Who Developed Progressive Disease or Relapsed While on Imatinib Mesylate

Conditions
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Gastrointestinal Cancer

Intervention / Treatment
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* Drug: AMG 706


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age ≥ 18 years; Disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) during previous treatment with imatinib mesylate at least 600 mg daily for at least 8 weeks, as per two independently assessed prestudy computerized tomography (CT) scans; Presence of at least one measurable (per RECIST) Progressing tumor lesion not previously treated with radiotherapy or embolization and evaluable by CT scan or magnetic resonance imaging (MRI); Karnofsky performance status ≥ 60; imatinib treatment terminated at least 7 days before study day 1; Adequate hepatic, renal, and cardiac function. Exclusion criteria: 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; cardiac disease including myocardial infarction, unstable angina, and congestive heart failure (New York Heart Association class > II), uncontrolled hypertension (systolic > 145 mmHg or diastolic > 85 mmHg), History of arterial thrombosis or deep vein thrombosis (including pulmonary embolus) within 1 year of study day 1; Absolute neutrophil count < 1.5x109/L, platelet count < 100x109/L, hemoglobin < 9.0 g/dL; Prior treatment with motesanib diphosphate or other KIT (except imatinib) or VEGF inhibitors. The study was approved by the institutional review board of each participating institution, and all patients provided written informed consent before any study-related procedures were performed.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm<br>AMG 125 mg daily continuously | Drug: AMG 706<br>* AMG 706 125 mg daily for 48 weeks, or until progressive disease or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate as defined using modified RECIST criteria. |  | 48 weeks treatment or until progressive disease, or unacceptable toxicity | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | time from randomization to progressive disease | 
| Overall survival |  | time to death | 
| Time to progression |  | time from response to progressive disease | 
| Time to response |  | time from first treatment to response | 
| Patient-reported outcomes |  | quality of life | 
| Use of opioid analgesics after minimal 6 months treatment |  | narcotics usage during study | 
| Objective response by PET and tumor size/density changes at week 8 |  | response rate at week 8 | 
| Objective response by size changes and/or target tumor density changes at week 8 |  | response rate at week 8 | 
| Safety Endpoints: Incidence of adverse events (including all, serious, grade 3, grade 4 and treatment related) |  | for duration of study | 
| Duration of response |  | time to respone to progression | 
| Palliative response |  | amelioration of symptoms | 
| Pharmacokinetic Endpoints: 1. The AMG 706 PK parameters (Cmax, t1/2, AUC0-24, C24); 2. To explore the PK/PD relationships |  | during specific study timepoints | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GIST