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Intracranial MeningiomaPhase 2NCT00972335

Trial of the Combination of Bevacizumab and Everolimus in Patients With Refractory, Progressive Intracranial Meningioma

A Phase 2 study testing Everolimus and Bevacizumab in people with Intracranial Meningioma, run by SCRI Development Innovations, LLC at 7 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

In this multicenter, Phase II trial, the investigators plan to evaluate the activity of the combination of bevacizumab and everolimus in patients with recurrent, progressive meningioma following maximal treatment with surgical resection and local radiation therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Intracranial Meningioma
What is being tested?
Everolimus and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
7 sitesUnited States
Study dates
Jan 2010to Jul 2014
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 be 18 years of age.
  • Histologic diagnosis of meningioma, WHO grade 1, 2, or 3 (benign, atypical, or malignant). In addition, patients with definitive radiologic evidence of meningioma who are unresectable, and in whom radiation therapy without biopsy is the standard treatment, are also eligible.
  • All patients must have developed recurrent disease/progression after receiving all standard treatments, which must include the following:
  • surgical resection, if possible;
  • definitive radiation therapy for unresectable meningioma, or for recurrent meningioma after resection.
  • patients must be at least 4 weeks post-surgery, and must be at least 2 weeks post-radiation therapy, with resolution of related toxicities.
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  • All patients must have progressive symptoms judged to be directly related to their recurrent/progressive meningioma. Patients with no new symptoms, or patients with stable neurologic deficits from previous surgical resection, are not eligible.
  • Patients may have had 0 or 1 previous systemic treatment regimens.
  • ECOG performance status of 0-2.
  • Adequate bone marrow, kidney, and liver function, as follows:
  • Absolute neutrophil count (ANC) ≥1500/μL
  • Hemoglobin (Hgb) ≥9 g/dL
  • Platelets ≥100,000/L (≤7 days prior to treatment)
  • AST or ALT ≤2.5 x institutional upper limit of normal (ULN)
  • Total bilirubin ≤1.5 x institutional ULN
  • Serum creatinine ≤1.5 x institutional ULN
  • Life expectancy of at least 12 weeks.
  • Ability to swallow whole pills.
  • Patients must have measurable disease on MRI scan.
  • Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
  • INR ≤1.5 x institutional upper limit of normal (ULN) . (Anticoagulation is allowed if target INR is ≤1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for >2 weeks at the time of study entry).
  • Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x institutional ULN. Note: In case one or both of these thresholds are exceeded, the patient can only be included in the study after initiation of appropriate lipid-lowering medication.
  • Patients must be accessible for treatment and follow-up.
  • Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.

Who cannot join

  • Previous treatment with bevacizumab or any other anti-angiogenesis agents.
  • Previous treatment with m-TOR inhibitors (sirolimus, temsirolimus, everolimus).
  • Patients who have had major surgery or significant traumatic injury within 4 weeks of the start of study drugs, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia), or patients that may require major surgery during the course of the study.
  • Minor surgical procedures (with the exception of the placement of portacath or other central venous access) must be completed at least 7 days prior to beginning protocol treatment.
  • Women who are pregnant or lactating.
  • Patients with proteinuria at screening as demonstrated by either:
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  • urine protein creatinine (UPC) ratio 1.0 at screening OR urine dipstick for proteinuria 2+ (patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection, and must demonstrate 1 g of protein/24 hours to be eligible)
  • Patients with a serious non-healing wound, active ulcer, or untreated bone fracture.
  • Patients with evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
  • Patients with history of hematemesis or hemoptysis (defined as having bright red blood of ½ teaspoon or more per episode) within 1 month prior to study enrollment.
  • History of myocardial infarction or unstable angina within 6 months of beginning treatment.
  • Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and /or diastolic blood pressure >100 mmHg while on antihypertensive medications).
  • New York Heart Association (NYHA) class II or greater congestive heart failure (CHF).
  • Serious cardiac arrhythmia requiring medication.
  • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of treatment.
  • History of stroke or transient ischemic attack within 6 months prior to beginning treatment.
  • Any prior history of hypertensive crisis or hypertensive encephalopathy.
  • History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 of beginning treatment.
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
  • Any severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study such as:
  • unstable angina pectoris, symptomatic CHF, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
  • severely impaired lung function
  • uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
  • active (acute or chronic) or uncontrolled severe infections
  • liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
  • Known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus), or to its excipients.
  • Immunization with attenuated live vaccines within 1 week of the study, or anytime during study treatment.
  • Chronic, systemic treatment with immunosuppressive agents. Patients who require a stable dose of corticosteroids for control of cerebral edema are eligible. Topical or inhaled steroids are also allowed.
  • Known human immunodeficiency virus (HIV) infection.
  • Grapefruits, star fruits, seville oranges, and their juices and products, should be avoided.
  • Drugs or substances known to be inhibitors or inducers of the isoenzyme CYP3A4 should be avoided.
  • Use of St. John's Wort or rifampicin.
  • Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
  • Use of any non-approved or investigational agent within 4 weeks of study entry. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
  • Other malignancies within the last 3 years, with the exception of adequately treated basal or squamous cell carcinomas of the skin, or carcinoma in situ of the cervix.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Norton Cancer Institute

    Louisville, Kentucky, 40207

  • UT Cancer Insititute Memphis

    Memphis, Tennessee, 38104

  • Tennessee Oncology, PLLC

    Nashville, Tennessee, 37023

  • Peninsula Cancer Institute

    Newport News, Virginia, 23601

  • Nebraska Methodist Cancer Center

    Omaha, Nebraska, 68114

  • Florida Hospital Cancer Insitute

    Orlando, Florida, 32804

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: A Phase II Trial of the Combination of Bevacizumab and Everolimus in Patients With Refractory, Progressive Intracranial Meningioma

In this multicenter, Phase II trial, the investigators plan to evaluate the activity of the combination of bevacizumab and everolimus in patients with recurrent, progressive meningioma following maximal treatment with surgical resection and local radiation therapy. Although these patients are relatively rare, there is currently no established standard of treatment for a disease that causes a great deal of morbidity, and that is eventually fatal.

Being tested
Everolimus, Bevacizumab
Keywords
Avastin, RAD001, Meningioma, Bevacizumab, Everolimus, Brain
Medical subject headings
Meningioma

What participants receive

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

  • EverolimusDrug

    Also called RAD001

    This drug will be dosed at 10 mg orally DAILY for the duration of the study.

  • BevacizumabDrug

    Also called Avastin

    This drug will be given IV at 10 mg/kg on Days 1 and 15 of each 28-day treatment cycle for the duration of the study.

Study groups in NCT00972335
Study groupRoleWhat they receive
Combination TherapyExperimentalEverolimus; this drug will be dosed at 10 mg orally DAILY for the duration of the study. Bevacizumab; this drug will be given IV at 10 mg/kg on Days 1 and 15 of each 28-day treatment cycle for the duration of the study
Receives: Drug: Everolimus; Drug: Bevacizumab

What is being measured

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

  1. Progression-free Survival (PFS), in the Treatment of Patients With Refractory Meningioma.

    Progression-free survival (PFS) is defined as the time from randomization until objective tumor progression (PD) or death. Progression is defined per MacDonald criteria for response as ≥25% increase in size of enhancing tumor or any new tumor on MRI scan, neurologically worse, and steroids stable or increased.

    Measured: 18 months

Secondary outcomes (2)

  1. To Evaluate the Toxicity of Bevacizumab/Everolimus in Patients With Recurrent Meningioma.

    Measured: 18 months

  2. To Correlate the Activity of This Treatment Regimen With Expression of Selected Intra-tumoral Biomarkers.

    Measured: 18 months

Timeline

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

  1. First posted4 Sep 2009 (estimated)
  2. Study startJan 2010
  3. Primary completionJul 2014
  4. Study completionJul 2014

Why it stopped: Study terminated early due to slow accrual

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
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00972335
Sponsor's protocol ID
SCRI CNS 12
Status last verified
Nov 2021
First submitted
2 Sep 2009
Last updated
10 Nov 2021
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus and Bevacizumab in people with Intracranial Meningioma, run by SCRI Development Innovations, LLC at 7 sites 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 24 inclusion and 36 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: stopped early, as of the sponsor's last update on 10 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites 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 4 Jun 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?

Progression-free Survival (PFS), in the Treatment of Patients With Refractory Meningioma. (time frame: 18 months). 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 NCT00972335.

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 Nov 2021.

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