SARC016: Study of Everolimus With Bevacizumab to Treat Refractory Malignant Peripheral Nerve Sheath Tumors
Condition: Malignant Peripheral Nerve Sheath Tumors; MPNST; Sarcoma
MeSH terms: Sarcoma; Nerve Sheath Neoplasms; Neurofibrosarcoma
Intervention: everolimus; bevacizumab
Intervention description: 10 mg tablet once daily; 10 mg/kg dose every 14 days
Intervention MeSH terms: Bevacizumab; Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MPNST; malignant peripheral nerve sheath tumors; RAD001; Everolimus; Bevacizumab; Sarcoma; Avastin; mTOR inhibitor

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