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AMG 102 and Avastin for Recurrent Malignant Glioma

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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.
  • - If sexually active, patients will take contraceptive measures for the duration of treatment as stated in the informed consent.

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 unless the patient has recovered from the toxic effects of such therapy.
  • - Treated with immunotherapeutic agents, vaccines, or MAb therapy within 4 weeks before enrollment unless the patient has recovered from the toxic effects of such therapy.
  • - Treated with alkylating agents within 4 weeks before enrollment or if the patient has been treated with daily or metronomic chemotherapy unless the patient has recovered from the toxic effects of such therapy.
  • - Treated with chemotherapy (non-alkylating agents) within 2 weeks before enrollment unless the patient has recovered from the toxic effects of such therapy.
  • - Less than 4 weeks after surgical resection of the brain tumor or less than 2 weeks after stereotactic biopsy before enrollment unless the patient has recovered from acute side effects of such procedures 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.
  • - 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.
  • - Pregnant (positive pregnancy test) or lactation.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT01113398
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Katy Peters
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Katherine B Peters, MD, PhDMary Lou Affronti, DNP ANP MHSc
Principal Investigator Affiliation Duke UniversityDuke University
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioblastoma Multiforme, Gliosarcoma
Study Website: View Trial Website
Arms & Interventions

Arms

Experimental: 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.

Interventions

Drug: - AMG 102

AMG 102 will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg every 2 weeks over 60 or 30 minutes.

Drug: - Avastin

Avastin will be administered as a continuous intravenous infusion at 10 mg/kg every 2 weeks (6-week study cycle) over 60 or 30 minutes. Avastin will be given prior to AMG 102.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Durham, North Carolina

Status

Address

The Preston Robert Tisch Brain Tumor Center

Durham, North Carolina, 27710