San Francisco, California 94115


Purpose:

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


Study summary:

OBJECTIVES: Primary - 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. Secondary - 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. Tertiary - 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.


Criteria:

DISEASE CHARACTERISTICS: - 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 available - 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 PATIENT CHARACTERISTICS: - 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 years - 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 hepatitis) - 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 PRIOR CONCURRENT THERAPY: - 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 vaccines - 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


NCT ID:

NCT00831324


Primary Contact:

Principal Investigator
Susan M. Chang, MD
University of California, San Francisco

Thelma Munoz
Phone: 415-353-2523
Email: munozt@neurosurg.ucsf.edu


Backup Contact:

N/A


Location Contact:

San Francisco, California 94115
United States

Clinical Trials Office - UCSF Helen Diller Family Comprehensi
Phone: 877-827-3222

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: October 09, 2019

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