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