A Phase II Study to Treat Advanced Malignant Glioma

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 61

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AMG 102 at 10 mg/kg Dose Level	AMG 102 at 10 mg/kg	Up to 40 subjects will be treated at this dose level based upon investigator assessment of responses observed.
AMG 102 at 20 mg/kg Dose Level	AMG 102 at 20 mg/kg	Up to 40 subjects will be treated at this dose level based upon investigator assessment of responses observed.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Assess the pharmacokinetics of AMG 102 in subjects with advanced malignant glioma	Weeks 1, 5, and 9
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