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

NCT00387400 | Completed Phase 1 DMC

• 3 other identifiers: I162CAN-NCIC-IND162CDR0000507616
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 9

Brief 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. 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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor; adult glioblastoma

Outcome Measures

Primary Outcomes (1)

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

  from the time of the first treatment

Secondary Outcomes (3)

• 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

  after every other course

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

  4 years

• Pharmacokinetics of everolimus during course 1

  during course 1

Interventions

everolimus DRUG

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

temozolomide DRUG

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

microarray analysis GENETIC

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 method OTHER

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.

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead

Study Sites (9)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

QEII Health Sciences Center

Halifax, Nova Scotia, B3H 1V7, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

Related Publications (1)

• 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.

  PMID: 22160854 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

Everolimus; Temozolomide; Microarray Analysis; Immunohistochemistry

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Microchip Analytical Procedures; Investigative Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Immunologic Techniques

Study Officials

• Warren P. Mason, MD

  Princess Margaret Hospital, Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2006
• First Posted: October 13, 2006
• Study Start: March 20, 2007
• Primary Completion: September 24, 2010
• Study Completion: January 6, 2012
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (9)