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Phase II Trial of RAD001 in Patients With Recurrent Low Grade Glioma

Phase 2
18 Years
Open (Enrolling)
Brain and Central Nervous System Tumors

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Trial Information

Phase II Trial of RAD001 in Patients With Recurrent Low Grade Glioma



- To determine the 6-month progression-free survival (PFS) of patients treated with
everolimus who were initially diagnosed with low-grade glioma and underwent biopsy or
subtotal resection at the time of recurrence with pathologic evidence of recurrent
low-grade glioma.


- To further describe the safety profile of this drug in these patients.

- To assess overall survival (OS) of patients treated with this drug.

- To assess the objective response rate in patients treated with this drug.

- To assess the correlation of phosphorylated PKB/Akt and PTEN expression with response,
progression status by 6 months, and OS of patients treated with this drug.


- To determine the 6-month PFS of patients treated with this drug who also underwent
prior radiotherapy.

OUTLINE: Patients receive oral everolimus once daily. Courses repeat every 8-12 weeks for up
to 2 years in the absence of disease progression or unacceptable toxicity. After completion
of study therapy, patients may continue treatment for as long as benefit is shown.

Previously collected tissue samples are analyzed by IHC for phosphorylated PKB/Akt status
and PTEN expression for correlation with study endpoints.

After completion of study treatment, patients are followed for 30 days.

Inclusion Criteria


- Histologically confirmed intracranial low-grade glioma* at initial diagnosis,
including any of the following histological subtypes:

- Astrocytoma

- No pilocytic astrocytomas

- Oligodendroglioma

- Mixed oligoastrocytoma NOTE: *Histologically confirmed progression to high-grade
gliomas are allowed provided patient has undergone prior radiotherapy

- Evaluable disease

- Unequivocal evidence of tumor recurrence or progression by histology and MRI, as
determined by the following:

- Histological review of pathology by an attending neuro-pathologist at the
University of California San Francisco (UCSF)

- Radiographic review of MRI* (performed within the past 14 days) by an attending
neuro-oncologist or neuro-radiologist at UCSF NOTE: *MRI must be performed after
≥ 5 days on a stable dose of steroids or a new baseline MRI is required

- Paraffin-embedded tissue samples acquired from surgery at time of recurrence must be

- No leptomeningeal or uncontrolled brain metastases, including those who require
glucocorticoids for their metastases

- Must be registered in University of California San Francisco Neuro-Oncology database


- Karnofsky performance status 60-100%

- Life expectancy > 8 weeks

- ANC ≥ 1.5 x 10^9/L

- Platelet count ≥ 100 x 10^9/L

- Hemoglobin > 9 g/dL

- Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)

- INR < 1.3 (or < 3 on anticoagulants)

- ALT and AST ≤ 2.5 times ULN

- Serum creatinine ≤ 1.5 times ULN

- Fasting serum cholesterol* ≤ 300 mg/dL OR ≤ 7.75 mmol/L

- Fasting triglycerides* ≤ 2.5 times ULN NOTE: *If one or both of these thresholds is
exceeded, the patient can only be included after initiation of appropriate lipid
lowering medication

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No significant medical illnesses that, in the opinion of the investigator, cannot be
adequately controlled with appropriate therapy, or would compromise the patient's
ability to tolerate study therapy

- No other cancer except nonmelanoma skin cancer or carcinoma in-situ of the cervix,
unless in complete remission and off all therapy for that disease within the past 3

- No active, bleeding diathesis

- No severe and/or uncontrolled medical conditions or other conditions that would
preclude participation in the study, including any of the following:

- NYHA class III-IV symptomatic congestive heart failure

- Unstable angina pectoris

- Myocardial infarction within the past 6 months

- Serious uncontrolled cardiac arrhythmia

- Other clinically significant cardiac disease

- Severely impaired lung function (i.e., oxygen [O_2] saturation 88% or less at
rest on room air by pulse oximetry must undergo further pulmonary function tests
to confirm normal pulmonary function and eligibility)

- Uncontrolled diabetes, defined by fasting serum glucose > 1.5 times ULN

- Active (acute or chronic) or uncontrolled severe infections

- Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent

- No impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of everolimus, including any of the following:

- Ulcerative disease

- Uncontrolled nausea

- Vomiting

- Diarrhea

- Malabsorption syndrome

- Small bowel resection

- No known HIV positivity

- No known hypersensitivity to everolimus or other rapamycins (i.e., sirolimus,
temsirolimus) or to its excipients

- No history of noncompliance to medical regimens

- Must be willing and able to comply with the protocol


- Recovered from all prior therapy

- Treatment for relapses prior to this recurrence allowed

- No prior therapy for this recurrence (e.g., radiotherapy)

- Supportive care (e.g., steroids or antiepileptics) does not constitute treatment
of recurrence)

- No prior mTOR inhibitor (i.e., sirolimus, temsirolimus, or everolimus)

- More than 5 days since prior enzyme-inducing antiepileptic agent

- More than 1 week since prior and no concurrent immunization with attenuated live

- Less than 4 months since prior surgical procedure for this recurrence

- At least 2 weeks since prior non-cytotoxic or biologic agents (e.g., interferon,
tamoxifen, thalidomide, or cis-retinoic acid)

- At least 4 weeks since prior radiotherapy

- At least 4 weeks since prior cytotoxic therapy (≥ 6 weeks since nitrosourea, 3 weeks
since procarbazine, and 2 weeks since vincristine)

- At least 4 weeks since prior and no concurrent investigational agent

- No other concurrent anticancer agents

- Concurrent enzyme-inducing antiepileptic agents allowed provided treatment is limited
to no more than 10 days during study

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival at 6 months

Outcome Time Frame:


Safety Issue:


Principal Investigator

Susan M. Chang, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, San Francisco


United States: Food and Drug Administration

Study ID:




Start Date:

January 2009

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult diffuse astrocytoma
  • adult pineal gland astrocytoma
  • adult subependymal giant cell astrocytoma
  • adult mixed glioma
  • adult anaplastic oligodendroglioma
  • adult oligodendroglioma
  • recurrent adult brain tumor
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115