Clinical trial NCT00089960: Study of AMG 706 in Subjects With Advanced Gastrointestinal Stromal Tumors (GISTs)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Cancer
Keywords: GIST
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2004-08-20
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate as defined using modified RECIST criteria.
timeFrame: 48 weeks treatment or until progressive disease, or unacceptable toxicity
Secondary outcomes:
measure: Progression-free survival
timeFrame: time from randomization to progressive disease
measure: Overall survival
timeFrame: time to death
measure: Time to progression
timeFrame: time from response to progressive disease
measure: Time to response
timeFrame: time from first treatment to response
measure: Patient-reported outcomes
timeFrame: quality of life
measure: Use of opioid analgesics after minimal 6 months treatment
timeFrame: narcotics usage during study
measure: Objective response by PET and tumor size/density changes at week 8
timeFrame: response rate at week 8
measure: Objective response by size changes and/or target tumor density changes at week 8
timeFrame: response rate at week 8
measure: Safety Endpoints: Incidence of adverse events (including all, serious, grade 3, grade 4 and treatment related)
timeFrame: for duration of study
measure: Duration of response
timeFrame: time to respone to progression
measure: Palliative response
timeFrame: amelioration of symptoms
measure: Pharmacokinetic Endpoints: 1. The AMG 706 PK parameters (Cmax, t1/2, AUC0-24, C24); 2. To explore the PK/PD relationships
timeFrame: during specific study timepoints
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.