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

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

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

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Cancer
• Intervention / Treatment: Drug: AMG 706

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm; AMG 125 mg daily continuously	Drug: AMG 706; AMG 706 125 mg daily for 48 weeks, or until progressive disease or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Benjamin RS, Schoffski P, Hartmann JT, Van Oosterom A, Bui BN, Duyster J, Schuetze S, Blay JY, Reichardt P, Rosen LS, Skubitz K, McCoy S, Sun YN, Stepan DE, Baker L. Efficacy and safety of motesanib, an oral inhibitor of VEGF, PDGF, and Kit receptors, in patients with imatinib-resistant gastrointestinal stromal tumors. Cancer Chemother Pharmacol. 2011 Jul;68(1):69-77. doi: 10.1007/s00280-010-1431-9. Epub 2010 Sep 14.

Helpful Links

• AmgenTrials clinical trials website
• Notice regarding posted summaries of trial results
• To access clinical trial results information click on this link

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: August 18, 2004
• First Submitted That Met QC Criteria: August 19, 2004
• First Posted (Estimate): August 20, 2004

Study Record Updates

• Last Update Posted (Estimate): April 29, 2013
• Last Update Submitted That Met QC Criteria: April 25, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: GIST
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Gastrointestinal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Motesanib diphosphate
• Other Study ID Numbers: 20040110