sarc016: study of everolimus with bevacizumab to treat refractory malignant peripheral nerve sheath tumors

Conditions: Malignant Peripheral Nerve Sheath Tumors; MPNST; Sarcoma

Summary: 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


Eligibility criteria:
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

Keywords: mpnst malignant peripheral nerve sheath tumors rad001 everolimus bevacizumab sarcoma avastin mtor inhibitor