AzTrials
AzTrials

Brain and Central Nervous System TumorsPhase 1NCT00387400

Temozolomide + Everolimus in Newly Diagnosed, Recurrent, or Progressive Malignant Glioblastoma Multiforme

A Phase 1 study testing everolimus, temozolomide and microarray analysis in people with Brain and Central Nervous System Tumors, run by NCIC Clinical Trials Group at 9 sites in Canada.

Completed

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

Official record
Search all trials

Trial summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Brain and Central Nervous System Tumors
What is being tested?
everolimus, temozolomide and microarray analysis
How many people
32 participants
Where
9 sitesCanada
Study dates
20 Mar 2007to 6 Jan 2012
Phase
Phase 1
Are there results?
None posted in the registry

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 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignant glioblastoma multiforme, meeting 1 of the following criteria:
  • Newly diagnosed disease AND meets the following criteria:
  • Has undergone prior surgery and radiotherapy with concurrent temozolomide
  • No prior chemotherapy except for concurrent low-dose temozolomide given with radiotherapy
  • Recurrent or progressive disease after front-line therapy AND meets the following criteria:
  • No more than 1 prior chemotherapy regimen in the adjuvant setting
  • More than 4 months since last adjuvant treatment
  • No prior chemotherapy for recurrence
  • Bidimensionally measurable disease, defined as ≥ 1 enhancing lesion ≥ 1 cm x 1 cm by CT scan or MRI, within 21 days of study entry (for patients with recurrent/relapsed disease)
  • Patients receiving steroids must be on stable dose for at least 14 days before baseline CT scan or MRI
  • Paraffin-embedded sample of primary or metastatic tumor diagnostic specimen must be available

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • Absolute granulocyte count ≥ 1,500/mm³
  • Platelet count ≥ 120,000/mm³
  • Bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No upper gastrointestinal condition or other condition that would preclude compliance with oral medication
  • No other prior malignancy except for adequately treated nonmelanoma skin cancer, curatively treated in situ cervical cancer, or other solid tumors curatively treated with no evidence of disease for the past 5 years
  • No serious illness or underlying medical condition that would preclude study compliance, including any of the following:
  • Significant neurologic or psychiatric disorder that would preclude obtaining informed consent
  • Active, ongoing infection
  • No known hypersensitivity to everolimus or temozolomide or their components

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 2 weeks since prior surgery and recovered
  • At least 4 weeks since prior radiotherapy
  • Concurrent enzyme-inducing antiepileptic drugs allowed
  • No concurrent inhibitors of cytochrome 3A4 (e.g., ketoconazole and similar antifungals, erythromycin, or diltiazem)
  • No other concurrent experimental drugs, anticancer treatment, or investigational therapy
  • No concurrent grapefruit juice

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Canada9 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • QEII Health Sciences Center

    Halifax, Nova Scotia, B3H 1V7

  • BCCA - Cancer Centre for the Southern Interior

    Kelowna, British Columbia, V1Y 5L3

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • CHUM - Hopital Notre-Dame

    Montreal, Quebec, H2L 4M1

  • McGill University - Dept. Oncology

    Montreal, Quebec, H2W 1S6

  • Univ. Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • BCCA - Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

Official title: A Phase I Study of Temozolomide and RAD001C in Patients With Malignant Glioblastoma Multiforme

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Giving temozolomide together with everolimus may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with temozolomide in treating patients with newly diagnosed, recurrent, or progressive malignant glioblastoma multiforme.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose(s) and the recommended phase II dose(s) of everolimus when administered with standard-dose temozolomide in patients with newly diagnosed, recurrent, or progressive glioblastoma multiforme.
  • Determine the toxicity of this regimen in these patients.

Secondary

  • Determine the efficacy of this regimen in patients with measurable disease at baseline.
  • Identify correlates of activity by molecular study of paraffin-embedded tumor samples from these patients.
  • Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a nonrandomized, nonblinded, parallel-group, multicenter, dose-escalation study of everolimus. Patients are stratified according to concurrent use of enzyme-inducing antiepileptic drugs (yes vs no).

Patients receive oral temozolomide once daily on days 2-5 in course 1 and on days 1-5 in all subsequent courses. Patients also receive oral everolimus once daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients with newly diagnosed disease receive up to 6 courses of treatment. Patients with recurrent disease who achieve a response (partial or complete response) or stable disease may continue treatment until disease progression or unacceptable toxicity.

Cohorts of 3-6 patients per stratum receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy. Once the MTD is determined, an additional 6 patients are treated at the MTD.

Patients' archival diagnostic tumor tissue is evaluated during study for correlative molecular studies (by immunohistochemical staining) of mammalian target of rapamycin inhibition status (mTOR activity) and pretreatment molecular markers. Blood samples are taken periodically during course 1 for pharmacokinetic studies.

After completion of study therapy, patients are followed at 4 weeks. Patients with stable or responding disease are then followed every 3 months until relapse or progression.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Keywords
adult giant cell glioblastoma, adult gliosarcoma, recurrent adult brain tumor, adult glioblastoma
Medical subject headings
Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma, Brain Neoplasms

What participants receive

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

  • everolimusDrug

    150 mg/m2/day PO Daily x 5, q 4 weeks

  • temozolomideDrug

    2.5 mg PO Daily, beginning day 2 of cycle 1, q 4 weeks

  • microarray analysisGenetic

    Tissue sections will be stained by immunohisto-chemistry using the following antibodies: EGFRvIII, PTEN, phospho-specific PKB/Akt Ser473; phosphor-mTORSer2448, p70S6K Thr389; S6 ribosomal protein Ser235/236. These antibodies are selected on the basis of providing a readout of upstream and downstream signaling through mTOR, and availability of antibodies that reliably stain paraffinembedded tissue.

  • immunohistochemistry staining methodOther

    Tissue sections will be stained by immunohisto-chemistry using the following antibodies: EGFRvIII, PTEN, phospho-specific PKB/Akt Ser473; phosphor-mTORSer2448, p70S6K Thr389; S6 ribosomal protein Ser235/236. These antibodies are selected on the basis of providing a readout of upstream and downstream signaling through mTOR, and availability of antibodies that reliably stain paraffinembedded tissue.

What is being measured

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

  1. Safety and tolerability of everolimus as measured by NCI CTCAE v3.0

    Measured: from the time of the first treatment

Secondary outcomes (3)

  1. Response as measured by CT scan and/or brain MRI at baseline and after every other course and clinical neurologic assessment at baseline and after every course

    Measured: after every other course

  2. Correlation of clinical outcome with pretreatment tumor tissue molecular markers as measured by molecular studies of paraffin-embedded tumor samples

    Assessed at study completion

    Measured: 4 years

  3. Pharmacokinetics of everolimus during course 1

    Measured: during course 1

Timeline

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

  1. First posted13 Oct 2006 (estimated)
  2. Study start20 Mar 2007
  3. Primary completion24 Sep 2010
  4. Study completion6 Jan 2012

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00387400
Sponsor's protocol ID
I162
Other IDs
CAN-NCIC-IND162, CDR0000507616
Status last verified
Apr 2020
First submitted
12 Oct 2006
Last updated
4 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Mason WP, Macneil M, Kavan P, Easaw J, Macdonald D, Thiessen B, Urva S, Lwin Z, McIntosh L, Eisenhauer E. A phase I study of temozolomide and everolimus (RAD001) in patients with newly diagnosed and progressive glioblastoma either receiving or not receiving enzyme-inducing anticonvulsants: an NCIC CTG study. Invest New Drugs. 2012 Dec;30(6):2344-51. doi: 10.1007/s10637-011-9775-5. Epub 2011 Dec 9.

    PubMed 22160854

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing everolimus, temozolomide and microarray analysis in people with Brain and Central Nervous System Tumors, run by NCIC Clinical Trials Group at 9 sites in Canada.

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

Who may be eligible to take part?

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 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Canada. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety and tolerability of everolimus as measured by NCI CTCAE v3.0 (time frame: from the time of the first treatment). 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 NCT00387400, which also lists 1 linked publication.

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 4 Aug 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in