A Phase II Study to Treat Advanced Malignant Glioma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the effectiveness and safety of AMG 102 for the treatment of Advanced Malignant Glioma.

Official Title
-----------------
A Multicenter, Open-label, Single Agent, Two-stage Phase 2 Study to Evaluate the Efficacy and Safety of AMG 102 in Subjects With Advanced Malignant Glioma

Conditions
-----------------
Advanced Malignant Glioma

Intervention / Treatment
-----------------
* Drug: AMG 102 at 20 mg/kg
* Drug: AMG 102 at 10 mg/kg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: subjects with documented histologically confirmed primary grade 4 advanced malignant glioma no more than 3 prior relapses or prior systemic treatments recurrent disease documented by MRI after prior therapy must have at least one site of bidimensionally measurable disease: archived tissue from the initial diagnosis of advanced malignant glioma or upon transformation to advanced malignant glioma are available for central review within approximately 4 weeks after enrollment age ≥ 18 years Karnofsky performance score ≥ 60% hemoglobin ≥ 10 g/dL absolute neutrophil count ≥ 1.5 x 10(9th)/L platelet count ≥ 100 x 10(9th)/L serum creatinine ≤ 1.5 times upper limit of normal alanine aminotransferase ≤ 2.5 times upper limit of normal serum total bilirubin ≤ 2.5 times upper limit of normal before any study-specific procedure, the appropriate written informed consent must be obtained Exclusion Criteria: history of central nervous system bleeding as defined by stroke or intraocular bleed (including embolic stroke) within 6 months before enrollment evidence of acute intracranial/intratumoral hemorrhage; except for subjects with stable grade 1 hemorrhage received radiation therapy within 4 weeks before enrollment or have not recovered from the toxic effects of such therapy treated previously with any c-Met or HGF targeted therapy treated with thalidomide or tamoxifen within 1 week before enrollment or has not recovered from the toxic effects of such cancer therapy treated with immunotherapeutic agents, vaccines or mAb therapy within 4 weeks before enrollment or have not recovered from the toxic effects of such cancer therapy treated with alkylating agents within 4 weeks before enrollment or has not recovered from the toxic effects of such cancer therapy treated with chemotherapy (non-alkylating agents) within 2 weeks before enrollment or has not recovered from the toxic effects of such cancer therapy surgical resection of brain tumor within 4 weeks before enrollment or have not recovered from acute side effects of such therapy, except for neurological effects plans to receive surgery, radiation therapy or other elective surgeries during the course of the study concurrent severe and/or uncontrolled medical disease (e.g., uncontrolled diabetes, congestive cardiac failure, myocardial infarction within 6 months before enrollment) that could compromise participation in the study active infection within 7 days before enrollment past or current history of another neoplasm, except for curatively treated non-melanoma skin cancer, carcinoma in situ of the cervix and other primary solid cancer with no known active disease present and no curative or adjuvant treatment administered for the last 3 years documented history of human immunodeficiency virus documented history of chronic viral hepatitis concurrent or prior (within 7 days of enrollment) anticoagulation therapy, except: Use of low molecular weight heparins (LMWH, e.g., enoxaparin sodium [Lovenox] and unfractionated heparin for prophylaxis against central venous catheter thrombosis is allowed Use of low dose warfarin (< 2 mg/day) for prophylaxis against central venous catheter thrombosis is allowed currently enrolled in or has not yet completed at least 30 days since ending other investigational device or therapeutic study(s) had major surgery within 4 weeks before enrollment or recovering from prior surgery known allergy or sensitivity to any of the excipients in the investigational product pregnant or breast feeding unwilling to use adequate contraceptive precautions during the course of the study and for 6 months after the last administration of investigational product, for: male subjects female subjects who are not post-menopausal (no menstrual period for a minimum of 12 months at study entry) or documented surgically sterile will not be bound to this exclusion previously treated with AMG 102 previously enrolled into this study will not be available for follow-up assessment has other disorders that compromises the ability of the subject to give written informed consent and/or comply with study procedures

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 102 at 10 mg/kg Dose Level<br>Up to 40 subjects will be treated at this dose level based upon investigator assessment of responses observed. | Drug: AMG 102 at 10 mg/kg<br>* AMG 102 at 10 mg/kg IV (in the vein) every 2 weeks<br>|
| Experimental: AMG 102 at 20 mg/kg Dose Level<br>Up to 40 subjects will be treated at this dose level based upon investigator assessment of responses observed. | Drug: AMG 102 at 20 mg/kg<br>* AMG 102 at 20 mg/kg IV (in the vein) every 2 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess best objective confirmed response rate in subjects with advanced malignant glioma receiving AMG 102 treatment |  | Week 9 from first dose of AMG 102 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety profile of AMG 102 in subjects with advanced malignant glioma |  | entire study | 
| Estimate overall survival and progression-free survival rates in this population |  | 8 week intervals | 
| Assess the duration of response and time to response in this population |  | Treatment Period | 
| Assess the pharmacokinetics of AMG 102 in subjects with advanced malignant glioma |  | Weeks 1, 5, and 9 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Glioma, Brain Tumor