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

NCT00972335 | Terminated Phase 2 Results

• 1 other identifier: SCRI CNS 12
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

Brief 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. 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.

Conditions

Intracranial Meningioma

Keywords

Avastin; RAD001; Meningioma; Bevacizumab; Everolimus; Brain

Outcome Measures

Primary Outcomes (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.

  18 months

Secondary Outcomes (2)

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

  18 months

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

  18 months

Study Arms (1)

Combination Therapy

EXPERIMENTAL

Everolimus; 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

Drug: Everolimus; Drug: Bevacizumab

Interventions

Everolimus DRUG

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

Also known as: RAD001

Combination Therapy

Bevacizumab DRUG

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.

Also known as: Avastin

Combination Therapy

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Genentech, Inc.: collaborator
• Novartis: collaborator

Study Sites (7)

Florida Hospital Cancer Insitute

Orlando, Florida, 32804, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

Nebraska Methodist Cancer Center

Omaha, Nebraska, 68114, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

UT Cancer Insititute Memphis

Memphis, Tennessee, 38104, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

Peninsula Cancer Institute

Newport News, Virginia, 23601, United States

Location

MeSH Terms

Conditions

Meningioma

Interventions

Everolimus; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Enrollment closed early due to slow accrual, leading to small number of subjects analyzed - biomarker analysis outcome measure not analyzed or reported

Results Point of Contact

• Title: John D Hainsworth, MD
• Organization: Sarah Cannon Research Institute

asksarah@scresearch.net

1-877-691-7274

Study Officials

• John D Hainsworth, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: 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

Study Record Dates

• First Submitted: September 2, 2009
• First Posted: September 4, 2009
• Study Start: January 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: November 10, 2021
• Results First Posted: June 4, 2015

Record last verified: 2021-11

Locations

US (7)