Phase II Study to Evaluate the Efficacy and Safety of AMG 102 and Avastin in Subjects With Recurrent Malignant Glioma
Overview
- Phase
- Phase 2
- Intervention
- AMG 102
- Conditions
- Glioblastoma Multiforme
- Sponsor
- Katy Peters
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Radiographic Response
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The primary purpose of the study is to assess the response rate of AMG 102 and Avastin treatment in subjects with advanced malignant glioma. Secondary objectives are to estimate overall survival and 6-month progression-free survival rates in this population and to assess the safety of this combination in this population.
Patients must have recurrent histologically confirmed diagnosis of World Health Organization (WHO) grade IV malignant glioma (glioblastoma multiforme or gliosarcoma) with no more than 3 prior progressions. Subjects will receive Avastin and AMG 102 every two weeks. Avastin will be administered prior to AMG 102. Up to 36 adult subjects will take part in this study at Duke.
In initial Phase I and II clinical trials, four potential Avastin-associated safety issues were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage. The most common side effect for AMG 102 have been nausea and fatigue.
Investigators
Katy Peters
Assistant Professor of Medicine
Duke University
Eligibility Criteria
Inclusion Criteria
- •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%.
- •An interval of at least 4 weeks between either prior tumor biopsy or prior major surgical procedure and study enrollment.
- •Bi-dimensionally measurable disease as assessed by magnetic resonance imaging.
- •Hemoglobin ≥9.0 g/dl, ANC ≥1500 cells/µl, Platelets ≥125,000 cells/µl (without transfusion within 14 days before enrollment).
- •Serum creatinine \< 1.5 mg/dl, bilirubin \< 1.5 times upper limit of normal, and serum SGOT (AST) and SGPT (ALT) \< 2.5 times upper limit of normal.
- •For patients on corticosteroids, they must be on a stable dose for 1 week prior to entry, and the dose should not be escalated over entry dose level, if clinically possible.
- •Signed informed consent approved by the Institutional Review Board.
- •No evidence of active CNS hemorrhage on the baseline MRI or CT scan.
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.
Arms & Interventions
AMG 102 with Avastin
Avastin will be administered as a continuous intravenous infusion at 10 mg/kg prior to AMG 102, which will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg. Subjects will receive infusions every 2 weeks.
Intervention: AMG 102
AMG 102 with Avastin
Avastin will be administered as a continuous intravenous infusion at 10 mg/kg prior to AMG 102, which will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg. Subjects will receive infusions every 2 weeks.
Intervention: Avastin
Outcomes
Primary Outcomes
Radiographic Response
Time Frame: 2 years
The percentage of participants with a complete or partial response as determined by modified Response Assessment in Neuro-Oncology (RANO) criteria will be determined. Complete Response (CR) is defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses) and accompanied by a stable or improving neurologic examination. Partial Response (PR) is defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids and accompanied by a stable or improving neurologic examination. Tumor assessments are done at baseline and the end of every 6-week cycle thereafter.
Secondary Outcomes
- Median Overall Survival (OS)(2 years)
- Six-month Progression-free Survival (PFS6)(6 months)
- Percentage of Participants Who Experience Treatment-related Grade 2 or Greater CNS Hemorrhage or Grade 4 or Greater Non-hematologic Toxicities(2 years)