Everolimus in Treating Patients With Recurrent or Progressive Low-Grade Glioma

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
Susan Chang, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00831324
First received: January 27, 2009
Last updated: January 17, 2014
Last verified: January 2014
  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.


Condition Intervention Phase
Brain Tumor
Drug: everolimus
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of RAD001 in Patients With Recurrent Low Grade Glioma

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Progression-free survival at 6 months [ Time Frame: months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response rate [ Time Frame: years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: years ] [ Designated as safety issue: No ]
  • Correlation of phosphorylated PKB/Akt and PTEN expression with response, progression status by 6 months, and overall response [ Time Frame: years ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: January 2009
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus
Targeted agent
Drug: everolimus Other: immunohistochemistry staining method Other: laboratory biomarker analysis

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00831324

Contacts
Contact: Thelma Munoz 415-353-2523 munozt@neurosurg.ucsf.edu

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi    877-827-3222      
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Susan M. Chang, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: Susan Chang, MD, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00831324     History of Changes
Other Study ID Numbers: CDR0000632931, UCSF-H7858-32860-01, 08109, CRAD001CUS58T
Study First Received: January 27, 2009
Last Updated: January 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
adult diffuse astrocytoma
adult pineal gland astrocytoma
adult subependymal giant cell astrocytoma
adult mixed glioma
adult anaplastic oligodendroglioma
adult oligodendroglioma
recurrent adult brain tumor

Additional relevant MeSH terms:
Brain Neoplasms
Glioma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 21, 2014