Clinical Trials for Adults | Phase II Study to Evaluate the Efficacy and Safety of AMG 102 and Avastin in Subjects with Recurrent Malignant Glioma
Purpose
- To assess the response rate of AMG 102 (C-Met inhibitor) and Avastin (anti-VEGF) treatment in subjects with advanced malignant glioma
- To estimate overall survival and 6-month progression-free survival rates in this population
- To assess the safety in this population
Eligibility, Inclusion
- Patients must have recurrent histologically confirmed diagnosis of WHO grade IV malignant glioma (glioblastoma multiforme or gliosarcoma) with no more than 3 prior progressions
- Age ≥ 18 years
- Karnofsky ≥ 60%
- At least 4 weeks between either prior tumor biopsy or prior major surgical procedure and study enrollment
- Measurable disease with no CNS hemorrhage as assessed by MRI or CT scan
- Lab parameters that meet eligibility criteria – CBC with diff, CMP, UA
- If sexually active, patients will take contraceptive measures for the duration of treatment
Exclusion Criteria
- Pregnancy or breast-feeding
- Baseline ECG with QTc > 0.45 second
- Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
- Thrombosis or vascular ischemic events within the last twelve months, such as deep venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral infarction, or myocardial infarction
- Active infection requiring IV antibiotics 7 days before enrollment
- 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 hemorrhage; except for subjects with stable grade 1 hemorrhage
- Less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 consecutive scans or histopathologic confirmation
- Treated previously with any c-Met or HGF targeted therapy
- Treated previously with VEGF or VEGFR therapies, including antibodies and tyrosine kinase inhibitors
- 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
- 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
- Concurrent or prior (within 7 days of enrollment) anticoagulation therapy, except: Use of low dose coumadin-type anticoagulants (≤ 2 mg PO QD) low molecular weight heparins (LMWH), e.g. Enoxaparin sodium (Lovenox) and unfractionated heparin for prophylaxis against central venous catheter thrombosis is allowed
- Grade 2 or greater peripheral edema or effusion (pleural, pericardial, or ascites)
- Inability to comply with study and/or follow-up procedure
- Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study
Avastin-Specific Exclusion Criteria (Subjects meeting any of the following criteria are ineligible for study entry)
- Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg)
- Prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- History of myocardial infarction or unstable angina within 6 months prior to Day 1, the day protocol therapy starts
- History of stroke or transient ischemic attack within 6 months prior to Day 1
- Significant vascular disease (e.g. aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) (within 6 months prior to Day 1)
- History of hemoptysis ( 1/2 teaspoon of bright red blood per episode) within 28 days prior to Day 1
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
- Serious, non-healing wound, active ulcer or untreated bone fracture
- Proteinuria as defined by > +1 on urinalysis dipstick
- Known hypersensitivity to any component of Avastin
Treatment Plan
- All treatments at Duke
- Infusions will be every other week (days 1,15 and 29 of each 42 day of cycle)
- Amgen 102 is provided free by Amgen
- Lab work every other week
- Return to clinic every 6 weeks and with MRI and ECG
- May receive treatment until tumor progresses, have too many toxicities, or want to come off study
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