Everolimus in Treating Patients With Recurrent Low-Grade Glioma
Condition: Adult Diffuse Astrocytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Neoplasm
MeSH terms: Glioma; Astrocytoma; Oligodendroglioma; Brain Neoplasms; Recurrence
Intervention: Everolimus; Archival Tissue Analysis
Intervention description: Given PO; Correlative studies
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well everolimus works in treating patients with recurrent
      low-grade glioma. Everolimus may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth or by blocking blood flow to the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a Karnofsky performance status of >= 60

          -  Patients must have a life expectancy > 8 weeks

          -  All patients must sign an informed consent document indicating that they are aware of
             the investigational nature of this study

          -  Patients must sign an authorization for the release of their protected health
             information

          -  Patients must have a magnetic resonance imaging (MRI) scan performed within 14 days
             prior to initial protocol treatment

          -  Patients must be registered in the University of California at San Francisco (UCSF)
             Neuro-Oncology database prior to treatment with study drug

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Hemoglobin (Hb) > 9 g/dL

          -  Serum bilirubin =< 1.5 x upper limit of normal (ULN)

          -  International normalized ratio (INR) < 1.5 (anticoagulation is allowed if target INR
             =< 1.5 on a stable dose of warfarin or on a stable dose of low molecular weight [LMW]
             heparin for > 2 weeks at the time of registration)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN

          -  Serum creatinine =< 1.5 x ULN

          -  Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =<
             2.5 x ULN; NOTE: In case one or both of these thresholds are exceeded, the patient can
             only be included after initiation of appropriate lipid lowering medication

          -  Patients must have histologically proven intracranial low-grade glioma at initial
             diagnosis; low-grade gliomas include: astrocytoma, oligodendroglioma and mixed
             oligoastrocytoma; pilocytic astrocytomas are excluded

          -  Patients must have unequivocal evidence for tumor recurrence or progression by
             histology as determined by review of pathology by an attending neuro-pathologist at
             UCSF

          -  If most recent histology shows progression to high grade glioma, patients must have
             had prior radiotherapy in order to be eligible

          -  Paraffin-embedded sections of tissue acquired from surgery at the time of suspected
             recurrence must be available for analysis

          -  Patients must have evidence for tumor recurrence or progression by MRI as determined
             by radiographic review of images by an attending neuro-oncologist or neuro-radiologist
             at UCSF

          -  If the steroid dose is increased between the date of the MRI and registration on the
             trial, a new baseline MRI is required; this MRI must be performed after >= 5 days on a
             stable dose of steroids

          -  An MRI must be used throughout the period of protocol treatment for tumor measurement

          -  Patients must have evaluable disease

          -  Patients may have had treatment (including radiotherapy) for any number of relapses
             prior to this recurrence

          -  Patients must be at least 4 weeks from the completion of any radiation therapy

          -  Patients must be less than 4 months from the surgical procedure for this recurrence

          -  Patients must have recovered from the toxic effects of prior therapy:

               -  4 weeks from any investigational agent

               -  4 weeks from prior cytotoxic therapy (except 6 weeks from nitrosoureas, 3 weeks
                  from procarbazine, 3 weeks from vincristine)

               -  3 weeks for non-cytotoxic or biologic agents e.g., interferon, tamoxifen,
                  thalidomide, cis-retinoic acid, tarceva, etc; note a 3-week washout is required
                  for prior treatment with bevacizumab

        Exclusion Criteria:

          -  Patients who have not recovered from the side effects of a major surgery or
             significant traumatic injury 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 corticosteroids, and treatment with low
             dose Decadron (=< 3 mg daily) are allowed

          -  Other than surgery, patients may not have therapy for this recurrence (including
             radiation); supportive care such as steroids or anti-epileptics does not constitute
             treatment of recurrence

          -  Patients must not have any significant medical illnesses that in the investigator?s
             opinion cannot be adequately controlled with appropriate therapy or would compromise
             the patient?s ability to tolerate this therapy

          -  Patients with a history of any other cancer (except for adequately treated carcinoma
             of the cervix or basal or squamous cell carcinomas of the skin), unless in complete
             remission and off of all therapy for that disease for a minimum of 3 years are
             ineligible

          -  Patients should not receive immunization with attenuated live vaccines within one week
             of study entry or during study period; close contact with those who have received
             attenuated live vaccines should be avoided during treatment with everolimus; examples
             of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio,
             Bacillus Calmette-Gu?rin (BCG), yellow fever, varicella and TY21a typhoid vaccines

          -  Uncontrolled brain or all leptomeningeal metastases, including patients who continue
             to require glucocorticoids for brain or leptomeningeal metastases

          -  Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study such as:

               -  Symptomatic congestive heart failure of New York heart Association Class III or
                  IV

               -  Unstable angina pectoris, symptomatic congestive heart failure, myocardial
                  infarction within 6 months of start of study drug, serious uncontrolled cardiac
                  arrhythmia or any other clinically significant cardiac disease

               -  Severely impaired lung function

               -  Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN (Note:
                  Optimal glycemic control should be achieved before starting trial therapy)

               -  Active (acute or chronic) or uncontrolled severe infections

               -  Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C)

          -  A Hepatitis B/C blood test must be done at screening for all patients; patients who
             test positive for Hepatitis C antibodies and the Hepatitis B antigen are ineligible

          -  A known history of human immunodeficiency virus (HIV) seropositivity

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled
             nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

          -  Impaired lung function: O2 saturation 88% or less at rest on room air by pulse
             oximetry; if O2 saturation is =< 88% at rest, further pulmonary function tests (PFTs)
             should be ordered to confirm normal pulmonary function and eligibility

          -  Patients with an active, bleeding diathesis

          -  Female patients who are pregnant or breast feeding, or adults of reproductive
             potential who are not using effective birth control methods; adequate contraception
             must be used throughout the trial and for 8 weeks after the last dose of study drug,
             by both sexes (women of childbearing potential [WOCBP] must have a negative urine or
             serum pregnancy test within 7 days prior to administration of RAD001)

          -  Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate
             contraception, during the study and for 8 weeks after the end of treatment

          -  Patients who have received prior treatment with an mammalian target of rapamycin
             (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus)

          -  Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins
             (e.g., sirolimus, temsirolimus) or to its excipients

          -  History of noncompliance to medical regimens

          -  Patients unwilling to or unable to comply with the protocol