Everolimus in Treating Patients With Recurrent Low-Grade Glioma

NCT00823459 | Completed Phase 2 Results

• 2 other identifiers: 08109NCI-2011-01701
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Adult Diffuse Astrocytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Neoplasm

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival at 6 Months.

  Number of patients alive without progressive disease at 6 months. Assessment of progression was defined by RANO as a 25% increase in the sum of all the products of measurable lesions, clear worsening of any evaluable disease or any new lesion

  At 6 months after treatment start

Secondary Outcomes (4)

• RAD001 Safety Profile in Patients With Recurrent LLG

  13 months

• Objective Response Rate (ORR) in Patients Treated With RAD001.

  12 months

• Overall Survival (OS) in Patients Treated With RAD001.

  Time from registration till death, an average of 5 years

• To Assess the Correlation of Activation of the PI3K/mTOR Pathway With Survival

  5 years

Study Arms (1)

Single-Arm Everolimus

EXPERIMENTAL

Single-arm study with patients receiving Everolimus orally once daily dosing of 10 mg continuously from Day 1 of study until progression of disease or unacceptable toxicity. In addition archival tissue will be analysed for markers of P13K/mTOR pathway activation.

Drug: Everolimus; Other: Archival Tissue Analysis

Interventions

Everolimus DRUG

Given PO

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress

Single-Arm Everolimus

Archival Tissue Analysis OTHER

Correlative studies

Single-Arm Everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Susan Chang: lead
• Novartis: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Astrocytoma; Glioma; Oligodendroglioma; Brain Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Susan Chang, MD
• Organization: University of California, San Francisco

jessica.carlson@ucsf.edu

(415) 353-2966

Study Officials

• Susan Chang, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Professor in Residence

Study Record Dates

• First Submitted: January 13, 2009
• First Posted: January 15, 2009
• Study Start: January 23, 2009
• Primary Completion: June 12, 2017
• Study Completion: November 13, 2017
• Last Updated: July 28, 2020
• Results First Posted: April 25, 2019

Record last verified: 2020-07

Locations

US (1)