Clinical trial NCT00427440: A Phase II Study to Treat 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Malignant Glioma
Keywords: Glioma
Brain Tumor
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2007-01-29
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effectiveness and safety of AMG 102 for the treatment of Advanced Malignant Glioma.


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

Primary outcomes:
measure: Assess best objective confirmed response rate in subjects with advanced malignant glioma receiving AMG 102 treatment
timeFrame: Week 9 from first dose of AMG 102
Secondary outcomes:
measure: To assess the safety profile of AMG 102 in subjects with advanced malignant glioma
timeFrame: entire study
measure: Estimate overall survival and progression-free survival rates in this population
timeFrame: 8 week intervals
measure: Assess the duration of response and time to response in this population
timeFrame: Treatment Period
measure: Assess the pharmacokinetics of AMG 102 in subjects with advanced malignant glioma
timeFrame: Weeks 1, 5, and 9
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Wen PY, Schiff D, Cloughesy TF, Raizer JJ, Laterra J, Smitt M, Wolf M, Oliner KS, Anderson A, Zhu M, Loh E, Reardon DA. A phase II study evaluating the efficacy and safety of AMG 102 (rilotumumab) in patients with recurrent glioblastoma. Neuro Oncol. 2011 Apr;13(4):437-46. doi: 10.1093/neuonc/noq198. Epub 2011 Feb 4.