Erlotinib Compared With Temozolomide or Carmustine in Treating Patients With Recurrent Glioblastoma Multiforme
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.
Brain and Central Nervous System Tumors
Drug: erlotinib hydrochloride
|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|
- Progression-free survival at 6 months [ Designated as safety issue: No ]
- 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 ]
|Study Start Date:||May 2004|
|Primary Completion Date:||March 2006 (Final data collection date for primary outcome measure)|
- 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.
|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|
|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|
|Glasgow, Scotland, United Kingdom, G11 6NT|
|Study Chair:||Martin J. van Den Bent, MD||Daniel Den Hoed Cancer Center at Erasmus Medical Center|