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Glioblastoma MultiformePhase 2NCT01113398

AMG 102 and Avastin for Recurrent Malignant Glioma

A Phase 2 study testing AMG 102 and Avastin in people with Glioblastoma Multiforme and Gliosarcoma, run by Katy Peters at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma Multiforme, Gliosarcoma
What is being tested?
AMG 102 and Avastin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
Aug 2010to Sep 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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 locations and contacts

1 site in 1 country.

United States1 site

  • The Preston Robert Tisch Brain Tumor Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

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

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.

Being tested
AMG 102, Avastin
Keywords
glioblastoma multiforme, gliosarcoma, malignant glioma, glioma, Avastin, bevacizumab, AMG 102, rilotumumab, recurrent, Duke, Pro00022491
Medical subject headings
Glioblastoma, Gliosarcoma, Glioma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AMG 102Drug

    Also called rilotumumab

    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.

  • AvastinDrug

    Also called Bevacizumab

    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.

Study groups in NCT01113398
Study groupRoleWhat they receive
AMG 102 with AvastinExperimentalAvastin 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.
Receives: Drug: AMG 102; Drug: Avastin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 years

Secondary outcomes (3)

  1. Median Overall Survival (OS)

    Overall survival is defined as the time in months from the start of protocol treatment until the date of death, or the date of last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.

    Measured: 2 years

  2. Six-month Progression-free Survival (PFS6)

    The percentage of participants alive and progression-free at 6 months after the start of study treatment will be determined. PFS6 will be calculated from the date study treatment started until the date of progression or death, or the date of last follow-up if participants are alive without progression. Kaplan-Meier methods will be used to estimate survival.

    Measured: 6 months

  3. Percentage of Participants Who Experience Treatment-related Grade 2 or Greater CNS Hemorrhage or Grade 4 or Greater Non-hematologic Toxicities

    The percentage of participants who experience unacceptable toxicity, defined as any treatment-related grade 2 or greater CNS hemorrhage or grade 4 or greater non-hematologic toxicity, will be calculated.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2010 (estimated)
  2. Study startAug 2010
  3. Primary completionNov 2014
  4. Study completionSep 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01113398
Sponsor's protocol ID
Pro00022491
Status last verified
Dec 2015
First submitted
28 Apr 2010
Last updated
10 Dec 2015
Data monitoring committee
No

Publications

  • 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.

    PubMed 29666296

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AMG 102 and Avastin in people with Glioblastoma Multiforme and Gliosarcoma, run by Katy Peters at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Radiographic Response (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01113398, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2015.

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