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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: carmustine
* Drug: erlotinib hydrochloride
* Drug: temozolomide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carmustine|nan|
|Drug: erlotinib hydrochloride|nan|
|Drug: temozolomide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival at 6 months |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 
| Severe toxic events assessed by CTCAE v3.0 at the end of each course |  |  | 
| Progression-free survival at 1 year |  |  | 
| Overall survival at 6 months and 1 year |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult glioblastoma, recurrent adult brain tumor, adult giant cell glioblastoma, adult gliosarcoma