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Adult Diffuse AstrocytomaPhase 2NCT00823459

Everolimus in Treating Patients With Recurrent Low-Grade Glioma

A Phase 2 study testing Everolimus and Archival Tissue Analysis in people with Adult Diffuse Astrocytoma and Adult Mixed Glioma, run by Susan Chang at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Everolimus and Archival Tissue Analysis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
1 siteUnited States
Study dates
23 Jan 2009to 13 Nov 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Patients must have unequivocal evidence for tumor recurrence or progression by histology as determined by review of pathology by an attending neuro-pathologist at UCSF
  • If most recent histology shows progression to high grade glioma, patients must have had prior radiotherapy in order to be eligible
  • Paraffin-embedded sections of tissue acquired from surgery at the time of suspected recurrence must be available for analysis
  • Patients must have evidence for tumor recurrence or progression by MRI as determined by radiographic review of images by an attending neuro-oncologist or neuro-radiologist at UCSF
  • If the steroid dose is increased between the date of the MRI and registration on the trial, a new baseline MRI is required; this MRI must be performed after >= 5 days on a stable dose of steroids
  • An MRI must be used throughout the period of protocol treatment for tumor measurement
  • Patients must have evaluable disease
  • Patients may have had treatment (including radiotherapy) for any number of relapses prior to this recurrence
  • Patients must be at least 4 weeks from the completion of any radiation therapy
  • Patients must be less than 4 months from the surgical procedure for this recurrence
  • Patients must have recovered from the toxic effects of prior therapy:
  • 4 weeks from any investigational agent
  • 4 weeks from prior cytotoxic therapy (except 6 weeks from nitrosoureas, 3 weeks from procarbazine, 3 weeks from vincristine)
  • 3 weeks for non-cytotoxic or biologic agents e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, tarceva, etc; note a 3-week washout is required for prior treatment with bevacizumab

Who cannot join

  • 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
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  • 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
  • A known history of human immunodeficiency virus (HIV) seropositivity
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Impaired lung function: O2 saturation 88% or less at rest on room air by pulse oximetry; if O2 saturation is =< 88% at rest, further pulmonary function tests (PFTs) should be ordered to confirm normal pulmonary function and eligibility
  • Patients with an active, bleeding diathesis
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods; adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug, by both sexes (women of childbearing potential [WOCBP] must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001)
  • Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
  • Patients who have received prior treatment with an mammalian target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus)
  • Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients
  • History of noncompliance to medical regimens
  • Patients unwilling to or unable to comply with the protocol

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California, San Francisco

    San Francisco, California, 94115

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine progression-free survival at 6 months associated with use of RAD001 (everolimus) in patients initially diagnosed with low-grade glioma who undergo biopsy or subtotal resection at the time of recurrence with pathologic evidence of recurrent low-grade glioma (LGG).

SECONDARY OBJECTIVES:

  1. To further delineate the safety profile of RAD001 in patients with recurrent LGG.
  2. To assess overall survival (OS) in patients treated with RAD001.
  3. To assess the objective response rate (ORR) in patients treated with RAD001.
  4. To assess the correlation of protein kinase B (PKB)/Akt and phosphatase and tensin homolog (PTEN) expression with response, progression status by 6 months, and OS in patients treated with RAD001.
Being tested
Everolimus, Archival Tissue Analysis
Medical subject headings
Astrocytoma, Glioma, Oligodendroglioma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Also called 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001

    Given PO

  • Archival Tissue AnalysisOther

    Correlative studies

Study groups in NCT00823459
Study groupRoleWhat they receive
Single-Arm EverolimusExperimentalSingle-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.
Receives: Drug: Everolimus; Other: Archival Tissue Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: At 6 months after treatment start

Secondary outcomes (4)

  1. RAD001 Safety Profile in Patients With Recurrent LLG

    Grade 4-5 treatment related adverse events as defined by CTCAE 3.0

    Measured: 13 months

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

    Objective response is defined as complete or partial response as defined by RANO criteria as determined by MRI and steroid requirement. Complete response was defined by disappearance of all measurable disease with minimal or no steroids; a partial response was defined as 50% in sum of all products in perpendicular diameters of all measurable lesions with no new lesions on stable or decreasing steroids.

    Measured: 12 months

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

    Number of years from the day the patient started treatment until the date of death, an average of 5 years.

    Measured: Time from registration till death, an average of 5 years

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

    Survival of patients with p-S6 staining of >19% (activated pathway)

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jan 2009 (estimated)
  2. Study start23 Jan 2009
  3. Primary completion12 Jun 2017
  4. Study completion13 Nov 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00823459
Sponsor's protocol ID
08109
Other IDs
NCI-2011-01701, 08109
Status last verified
Jul 2020
First submitted
13 Jan 2009
Last updated
28 Jul 2020

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus and Archival Tissue Analysis in people with Adult Diffuse Astrocytoma and Adult Mixed Glioma, run by Susan Chang at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival at 6 Months. (time frame: At 6 months after treatment start). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00823459.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2020.

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