Randomized Phase II of TARCEVA™ (Erlotinib) Versus Temozolomide Or BCNU in Patients With Recurrent Glioblastoma Multiforme
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
Randomized Phase II of TARCEVA™ (Erlotinib) Versus Temozolomide Or BCNU in Patients With Recurrent Glioblastoma Multiforme
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression-free survival at 6 months
Safety Issue:
No
Principal Investigator
Martin J. van Den Bent, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Daniel Den Hoed Cancer Center at Erasmus Medical Center
Authority:
United States: Federal Government
Study ID:
EORTC-26034-16031
NCT ID:
NCT00086879
Start Date:
May 2004
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- adult glioblastoma
- recurrent adult brain tumor
- adult giant cell glioblastoma
- adult gliosarcoma
- Glioblastoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
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