AMG 102 and Avastin for Recurrent Malignant Glioma

NCT01113398 | Completed Phase 2 Results

• 1 other identifier: Pro00022491
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma Multiforme; Gliosarcoma

Keywords

glioblastoma multiforme; gliosarcoma; malignant glioma; glioma; Avastin; bevacizumab; AMG 102; rilotumumab; recurrent; Duke; Pro00022491

Outcome Measures

Primary Outcomes (1)

• Radiographic Response

  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.

  2 years

Secondary Outcomes (3)

• 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

Study Arms (1)

AMG 102 with Avastin

EXPERIMENTAL

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.

Drug: AMG 102; Drug: Avastin

Interventions

AMG 102 DRUG

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.

Also known as: rilotumumab

AMG 102 with Avastin

Avastin DRUG

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.

Also known as: Bevacizumab

AMG 102 with Avastin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Katy Peters: lead
• Amgen: collaborator

Study Sites (1)

The Preston Robert Tisch Brain Tumor Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Affronti ML, Jackman JG, McSherry F, Herndon JE 2nd, Massey EC Jr, Lipp E, Desjardins A, Friedman HS, Vlahovic G, Vredenburgh J, Peters KB. Phase II Study to Evaluate the Efficacy and Safety of Rilotumumab and Bevacizumab in Subjects with Recurrent Malignant Glioma. Oncologist. 2018 Aug;23(8):889-e98. doi: 10.1634/theoncologist.2018-0149. Epub 2018 Apr 17.

  PMID: 29666296 DERIVED

Related Links

• The Preston Robert Tisch Brain Tumor Center

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Glioma; Recurrence

Interventions

rilotumumab; Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

11/21/14 Amgen notified PI they stopped their own AMG102 studies due to increased risk found in the TX arm on a different study. Dr. Peters decided to stop TX on the 3 current subjects on her study at that time although no increased risks were found.

Results Point of Contact

• Title: Katherine B. Peters, MD, PhD
• Organization: Duke University Medical Center

katy.peters@duke.edu

919-684-6173

Study Officials

• Katherine B Peters, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

• Mary Lou Affronti, DNP ANP MHSc

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: April 28, 2010
• First Posted: April 29, 2010
• Study Start: August 1, 2010
• Primary Completion: November 1, 2014
• Study Completion: September 1, 2015
• Last Updated: December 10, 2015
• Results First Posted: December 10, 2015

Record last verified: 2015-12

Locations

US (1)