Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas
Condition: Glioma; Low-grade Glioma; Astrocytoma
MeSH terms: Glioma; Astrocytoma
Intervention: everolimus
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 3 Years
Maximum age: 21 Years
Healthy volunteers: No
Keywords: RAD001

Summary:

      The purpose of this research study is to learn if the study drug RAD001 can shrink or slow
      the growth of low-grade gliomas. Additionally, the safety of RAD001 will be studied. RAD001
      is a drug that may act directly on tumor cells by inhibiting tumor cell growth and
      proliferation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologic verification of one of the eligible diagnoses listed
             here: Astrocytoma variants; fibrillary, protoplasmic, mixed: Pilocytic astrocytoma;
             including pilomyxoid variants: Pleomorphic xanthoastrocytoma: infantile desmoplastic
             astrocytoma: ganglioglioma: oligodendroglial tumors: mixed glioma.

          -  Patients must have received at least one cancer-directed therapy and patients with
             allergies to carboplatin must have demonstrated progressive disease after cessation of
             therapy.

          -  Must have at least one measurable site of disease that has not been previously
             irradiated. If the patient has previous irradiation to the marker lesion(s), there
             must be evidence of progression since radiation treatment.

          -  Patients must be between 3 years of age and 21 years of age

          -  Karnofsky Performance Status of 50% or greater for patients less than 10 years of age
             or Lansky Score of 50% or greater for patients 10 and up.

          -  Participants must have recovered from the acute toxic effects of all prior
             chemotherapy or radiotherapy prior to entering the study. Refer to protocol for
             specific time restrictions with prior therapy completion.

          -  Adequate bone marrow function as defined in protocol

          -  Adequate renal function as defined in protocol

          -  Adequate liver function as defined in protocol

          -  Patients must have a fasting LDL cholesterol within the normal range per institutional
             guidelines

          -  Patients taking cholesterol lowering agent must be on a single medication and on a
             stable dose for at least 4 weeks

          -  Fasting serum cholesterol as outlined in protocol

          -  Patients must not be taking enzyme-inducing anticonvulsants

          -  Patients may not be currently receiving strong inhibitors of CYP3A4

        Exclusion Criteria:

          -  Presence of NF1 by clinical examination or by genetic testing

          -  Patients who have had a major surgery or significant traumatic injury within 2 weeks
             of start of study drug, patients who have not recovered from teh side effects of any
             major surgery, or patients that may require major surgery during the course of the
             study

          -  Patients receiving chronic, systemic treatment with corticosteroids or another
             immunosuppressive agent. Topical or inhaled are allowed

          -  Evidence of plexiform neurofibroma, malignant peripheral nerve sheath tumor, or other
             cancer requiring treatment with chemotherapy or radiation therapy

          -  Uncontrolled brain or leptomeningeal metastases from plexiform neurofibromas,
             malignant peripheral nerve sheath tumors, or other cancers (other than astrocytoma
             variants; fibrillary, protoplasmic, mixed: Pilocytic astrocytoma; including pilomyxoid
             variants: Pleomorphic xanthoastrocytoma: infantile desmoplastic astrocytoma:
             ganglioglioma: oligodendroglial tumors: mixed glioma), including patients who continue
             to require glucocorticoids for control of symptoms related to brain or leptomeningeal
             metastases.

          -  Other malignancies within the past three 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 (see protocol for
             examples)

          -  Known history of HIV seropositivity

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of RAD001

          -  Active, bleeding diathesis or oral anti-vitamin K medication (except low dose
             coumarin)

          -  Female patients who are pregnant or breast feeding

          -  Prior treatment with an mTOR inhibitor

          -  Known hypersensitivity to RAD001 or other rapamycins or to is excipients

          -  Dental braces or prosthesis that interferes with tumor imaging

          -  Patients with a positive history of Hepatitis B or Hepatitis C

          -  Patients should not receive immunization with attenuated live vaccines within one week
             of study entry or during study period.