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AMG 102 and Avastin for Recurrent Malignant Glioma

Information source: Duke University
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Glioblastoma Multiforme; Gliosarcoma

Intervention: AMG 102 (Drug); Avastin (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Katy Peters

Official(s) and/or principal investigator(s):
Katherine B Peters, MD, PhD, Principal Investigator, Affiliation: Duke University
Mary Lou Affronti, DNP, RN, MSN, ANP, MHSc, Principal Investigator, Affiliation: Duke University

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.

Clinical Details

Official title: Phase II Study to Evaluate the Efficacy and Safety of AMG 102 and Avastin in Subjects With Recurrent Malignant Glioma

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Radiological response rates

Secondary outcome:

Overall Survival and 6-month progression-free survival

Incidence and severity of CNS hemorrhage and systemic hemorrhage; Incidence of grade 4 or greater hematologic and grade 3 or greater non-hematologic toxicities

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Locations and Contacts

The Preston Robert Tisch Brain Tumor Center, Durham, North Carolina 27710, United States
Additional Information

The Preston Robert Tisch Brain Tumor Center

Starting date: August 2010
Last updated: March 12, 2015

Page last updated: August 20, 2015

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