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

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

- 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