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Randomized Phase II of TARCEVA™ (Erlotinib) Versus Temozolomide Or BCNU in Patients With Recurrent Glioblastoma Multiforme

Phase 2
18 Years
Not Enrolling
Brain and Central Nervous System Tumors

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Trial Information

Randomized Phase II of TARCEVA™ (Erlotinib) Versus Temozolomide Or BCNU in Patients With Recurrent Glioblastoma Multiforme



- 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

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

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

Inclusion Criteria


- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival at 6 months

Safety Issue:


Principal Investigator

Martin J. van Den Bent, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Daniel Den Hoed Cancer Center at Erasmus Medical Center


United States: Federal Government

Study ID:




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