A Phase II Trial of the Combination of Bevacizumab and Everolimus in Patients With Refractory, Progressive Intracranial Meningioma
Overview
- Phase
- Phase 2
- Intervention
- Everolimus
- Conditions
- Intracranial Meningioma
- Sponsor
- SCRI Development Innovations, LLC
- Enrollment
- 18
- Locations
- 7
- Primary Endpoint
- Progression-free Survival (PFS), in the Treatment of Patients With Refractory Meningioma.
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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-
- •Adequate bone marrow, kidney, and liver function, as follows:
Exclusion Criteria
- •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.
Arms & Interventions
Combination Therapy
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
Intervention: Everolimus
Combination Therapy
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
Intervention: Bevacizumab
Outcomes
Primary Outcomes
Progression-free Survival (PFS), in the Treatment of Patients With Refractory Meningioma.
Time Frame: 18 months
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.
Secondary Outcomes
- 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)