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Erlotinib Compared With Temozolomide or Carmustine in Treating Patients With Recurrent Glioblastoma Multiforme

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00086879
Recruitment Status : Completed
First Posted : July 12, 2004
Last Update Posted : July 27, 2017
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary:

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as temozolomide and carmustine, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether erlotinib is more effective than temozolomide or carmustine in treating recurrent glioblastoma multiforme.

PURPOSE: This randomized phase II trial is studying erlotinib to see how well it works compared to temozolomide or carmustine in treating patients with recurrent glioblastoma multiforme.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: carmustine Drug: erlotinib hydrochloride Drug: temozolomide Phase 2

Detailed Description:



  • Compare the therapeutic activity of erlotinib vs temozolomide or carmustine in patients with recurrent glioblastoma multiforme.
  • Compare 6-month progression-free survival in patients treated with these drugs.


  • Compare the safety of these drugs in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral erlotinib* once daily on day 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients treated with enzyme inducing anti-epileptic drugs (EIAEDs) receive a higher dose of erlotinib than patients not receiving any anti-epileptic drugs or EIAEDs.

  • Arm II: Patients who have not received prior temozolomide are assigned to receive temozolomide. Patients who have received prior temozolomide are assigned to receive carmustine. Patients receive 1 of the following treatment regimens:

    • Patients receive oral temozolomide* once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    • Patients receive carmustine IV once daily on days 1-3. Treatment repeats every 56 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Chemotherapy-naïve patients receive a higher dose of temozolomide than patients who have received prior adjuvant chemotherapy.

Patients are followed every 8 weeks until disease progression and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 100-110 patients (50-55 per treatment arm) will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II of TARCEVA™ (Erlotinib) Versus Temozolomide Or BCNU in Patients With Recurrent Glioblastoma Multiforme
Study Start Date : May 2004
Actual Primary Completion Date : March 2006
Actual Study Completion Date : March 2011

Primary Outcome Measures :
  1. Progression-free survival at 6 months

Secondary Outcome Measures :
  1. Response (complete [CR] or partial response [PR]) measured by McDonald's criteria at least 4 weeks after first documented response and every 8 weeks until disease progression or until start of another treatment
  2. Severe toxic events assessed by CTCAE v3.0 at the end of each course
  3. Progression-free survival at 1 year
  4. Overall survival at 6 months and 1 year

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed glioblastoma multiforme

    • Some oligodendroglial elements allowed provided they make up < 25% of the tumor
  • Recurrent disease documented by MRI after prior radiotherapy
  • At least 1 bidimensionally measurable target lesion ≥ 2 cm by MRI
  • Undergone prior surgery for recurrent primary brain tumor more than 3 months before study entry

    • Must have a clearly limited target lesion ≥ 2 cm OR evidence of progressive and measurable target lesion OR a second measurable target lesion outside the surgical area



  • Over 18

Performance status

  • Karnofsky 70-100%

Life expectancy

  • Not specified


  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm ^3


  • AST and ALT < 2.5 times upper limit of normal (ULN)
  • Bilirubin < 1.5 times ULN


  • Creatinine < 1.5 times ULN


  • Clinically normal cardiac function
  • No ischemic heart disease within the past 12 months
  • No New York Heart Association grade III or IV cardiac insufficiency
  • No unstable angina
  • No arryhthmia


  • DLCO > 70% of predicted (for patients randomized to receive erlotinib [arm I] or carmustine [arm II])
  • No history of pulmonary disease that would affect pulmonary function including any of the following:

    • Chronic bronchopneumopathy
    • Pleural effusion
    • Interstitial pnuemonia
    • Pulmonary lymphangitis


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • No other malignancy except cone biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer
  • No psychological, familial, sociological, or geographical factors that would preclude study compliance


Biologic therapy

  • No prior HER-targeted agents
  • No concurrent growth factors for neutrophil count elevation
  • No concurrent epoetin alfa


  • Prior adjuvant temozolomide allowed
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
  • No more than 1 prior adjuvant chemotherapy regimen
  • No prior chemotherapy for recurrent disease

Endocrine therapy

  • Must be on a stable or decreasing dose of corticosteroids for at least 2 weeks before study entry


  • See Disease Characteristics
  • More than 3 months since prior radiotherapy to the brain
  • No prior high-dose radiotherapy (> 65 Gy), stereotactic radiosurgery, or internal radiotherapy unless disease recurrence confirmed


  • See Disease Characteristics


  • No prior participation in experimental therapies
  • No concurrent CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, troleandomycin, cimetidine, or grapefruit juice)
  • No concurrent warfarin or other coumarin derivatives

    • Concurrent low-molecular weight heparin allowed
  • No other concurrent investigational drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00086879

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U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Dijon, France, 21079
Centre Regional Rene Gauducheau
Nantes-Saint Herblain, France, 44805
Centre Antoine Lacassagne
Nice, France, 06189
CHU Pitie-Salpetriere
Paris, France, 75651
Institut Gustave Roussy
Villejuif, France, F-94805
Azienda Ospedaliera di Padova
Padova, Italy, 35128
Medisch Centrum Haaglanden
's-Gravenhage, Netherlands, 2501 CK
University Medical Center Rotterdam at Erasmus Medical Center
Rotterdam, Netherlands, 3000 CA
United Kingdom
Western Infirmary
Glasgow, Scotland, United Kingdom, G11 6NT
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
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Study Chair: Martin J. van Den Bent, MD Daniel Den Hoed Cancer Center at Erasmus Medical Center
Publications of Results:
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Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC Identifier: NCT00086879    
Other Study ID Numbers: EORTC-26034-16031
First Posted: July 12, 2004    Key Record Dates
Last Update Posted: July 27, 2017
Last Verified: July 2017
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
adult glioblastoma
recurrent adult brain tumor
adult giant cell glioblastoma
adult gliosarcoma
Additional relevant MeSH terms:
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Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents