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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00086879
First received: July 8, 2004
Last updated: September 20, 2012
Last verified: September 2012
  Purpose

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 Intervention Phase
Brain and Central Nervous System Tumors
Drug: carmustine
Drug: erlotinib hydrochloride
Drug: temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II of TARCEVA™ (Erlotinib) Versus Temozolomide Or BCNU in Patients With Recurrent Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Progression-free survival at 6 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Designated as safety issue: No ]
  • Severe toxic events assessed by CTCAE v3.0 at the end of each course [ Designated as safety issue: Yes ]
  • Progression-free survival at 1 year [ Designated as safety issue: No ]
  • Overall survival at 6 months and 1 year [ Designated as safety issue: No ]

Enrollment: 110
Study Start Date: May 2004
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • Over 18

Performance status

  • Karnofsky 70-100%

Life expectancy

  • Not specified

Hematopoietic

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

Hepatic

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

Renal

  • Creatinine < 1.5 times ULN

Cardiovascular

  • 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

Pulmonary

  • 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

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

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

Chemotherapy

  • 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

Radiotherapy

  • 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

Surgery

  • See Disease Characteristics

Other

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086879

Locations
Belgium
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
France
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
Italy
Azienda Ospedaliera di Padova
Padova, Italy, 35128
Netherlands
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
Investigators
Study Chair: Martin J. van Den Bent, MD Daniel Den Hoed Cancer Center at Erasmus Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00086879     History of Changes
Other Study ID Numbers: EORTC-26034-16031, EORTC-26034-16031
Study First Received: July 8, 2004
Last Updated: September 20, 2012
Health Authority: United States: Federal Government

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:
Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Carmustine
Temozolomide
Dacarbazine
Erlotinib
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014