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

Brain Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00831324
• Other study ID #: CDR0000632931
• Secondary ID: UCSF-H7858-32860
• Status: Recruiting
• Phase: Phase 2
• First received: January 27, 2009
• Last updated: May 27, 2015
• Start date: January 2009
• Est. completion date: January 2017

Study information

• Verified date: May 2015
• Source: University of California, San Francisco
• Contact: Thelma Munoz
• Phone: 415-353-2523
• Email: munozt[@]neurosurg.ucsf.edu
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 2017
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumor

Intervention

Drug:
• everolimus

Other:
• immunohistochemistry staining method

• laboratory biomarker analysis

Locations

Country	Name	City	State
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival at 6 months		months	No
Secondary	Objective response rate		years	No
Secondary	Overall survival		years	No
Secondary	Correlation of phosphorylated PKB/Akt and PTEN expression with response, progression status by 6 months, and overall response		years	No