SARC016: Study of Everolimus With Bevacizumab to Treat Refractory Malignant Peripheral Nerve Sheath Tumors

Phase 2 Study of the mTOR Inhibitor Everolimus in Combination With Bevacizumab in Patients With Sporadic and Neurofibromatosis Type 1 (NF1) Related Refractory Malignant Peripheral Nerve Sheath Tumors

To determine the clinical response rate of everolimus in combination with bevacizumab for patients with chemotherapy refractory sporadic or neurofibromatosis type 1 (NF1) associated malignant peripheral nerve sheath tumor (MPNST). To evaluate the toxicity and safety of everolimus in combination with bevacizumab in individuals with MPNST

Inclusion Criteria:

• Patients 18 or older
• Unresectable or metastatic sporadic or NF1 associated high-grade MPNST
• Experienced progression after one or more prior regimens of cytotoxic chemotherapy
• Patients must be able to swallow tablets
• Patients must have measurable disease, defined as at least one tumor that is measurable
• Patients who develop a recurrence or progression (WHO criteria) of an MPNST in a previously radiated field may be enrolled if it has been at least 4 weeks since the last dose of radiation therapy
• Patients must have recovered from the toxic effects of all prior therapy before entering this study
• Adequate organ function
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Patents who received an anthracycline prior to enrollment must have an ejection fraction ≥ 50%
• Subjects of childbearing potential requires acceptable form of birth control
• Informed consent

Exclusion Criteria:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 3 weeks of the start of study drug or patients receiving prior treatment with investigational drugs 4 weeks of the start of study drug
• Patients may not be currently receiving strong inhibitors of CYP3A4, and may not have received these medications within 1 week of entry
• Prior radiotherapy within 4 weeks of the start of study drug
• Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug,
• Patients who have not recovered from the side effects of any major surgery
• Patients that may require major surgery during the course of the study
• Less than 7 days have passed from core biopsies or other minor surgical procedures excluding placement of a vascular access device
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent(Topical or inhaled corticosteroids are allowed)
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
• Female patients who are pregnant or breast feeding
• Patients who have received prior treatment with an mTOR inhibitor or bevacizumab
• Patients with known hypersensitivity to rapamycins
• concurrent use of anti-coagulant drugs
• Patients using Seville orange, star fruit, grapefruit and their juices, and St. John's Wort
• Patients taking enzyme inducing anticonvulsants