The Effects of Continuous 28-day (28/28) Temozolomide Chemotherapy in Subjects With Recurrent Malignant Glioma Who Have Failed the Conventional 5-day (5/28) Treatment (P04601)

The purpose of this non-randomized, open-label, multicenter, Phase II, 2-stage design, RESCUE study is to test the hypothesis that continuous 28-day oral dosing (28/28) with dose-intense temozolomide (50 mg/m\^2) for up to 12 months may overcome resistance and be effective in the management of adult patients with malignant glioma who have failed following at least 2 cycles (2 months) of conventional 5-day (5/28) cycles of high-dose temozolomide (150-200 mg/m\^2).


Eligibility Criteria:
Inclusion Criteria:

* Adult patients, greater than 18 years old.
* Surgically confirmed diagnosis of malignant glioma, specifically anaplastic glioma (anaplastic astrocytoma \[AA\], anaplastic oligodendroglioma \[AO\], anaplastic oligoastrocytoma \[AOA\]) or glioblastoma multiforme (GBM).
* Must have completed at least 2 cycles (2 months) of conventional 5/28 temozolomide, with radiological evidence of progression.
* GBM treated with concurrent chemoradiation with temozolomide according to the EORTC/NCIC (European Organization for Research \& Treatment of Cancer/National Cancer Institute of Canada) protocol.
* Evidence of progression confirmed radiologically (CT \[computed tomography\] or MRI \[magnetic resonance imaging\]).
* Patients must be enrolled within 2 weeks of last radiological confirmation of progression, except for patients undergoing surgical resection.
* Patients undergoing surgical resection for recurrent disease must be enrolled within 2 weeks of the post-surgical scan.
* Patients with no residual disease after surgery are allowed.
* Steroids dose should have been stabilized during the last 2 weeks prior to enrollment.
* Use of medically approved contraception in fertile males and females.
* Women of childbearing potential must have a negative urine or serum pregnancy test (urinary excretion or serum level of bHCG \[beta human chorionic gonadotropin\]) within 24 hours of inclusion in the study.
* Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
* Signed informed consent form.

Exclusion Criteria:

* GBM progression during the first 2 months of adjuvant temozolomide (5/28).
* AA progression during the first 2 months of standard temozolomide therapy (5/28).
* Chemotherapy for the malignant glioma other than temozolomide.
* More than one prior course of chemotherapy with temozolomide.
* Patient evolving from anaplastic glioma to GBM following primary therapy.
* Patient older than 70 years or who received no conventional chemoradiation regimen.
* Patient who received radiotherapy for recurrent disease.
* Patient with metastatic disease.
* Known human immunodeficiency virus (HIV) infection.
* History of non-compliance to other therapies.
* Inadequate hematological, renal and hepatic function according to all of the following laboratory values (to be performed within 14 days, inclusive, prior to study inclusion):
* Absolute neutrophil count \<=1.5 ×10\^9/L;
* Platelets \<=100 ×10\^9/L;
* Hemoglobin \<90 g/L;
* Serum creatinine \>=1.5 times upper limit of laboratory normal (ULN);
* Total serum bilirubin \>=1.5 times ULN;
* ASAT (AST \[aspartate aminotransferase\]) or ALAT (ALT \[alanine aminotransferase) \>2.0 times ULN;
* Alkaline phosphatase of \>2.5 times ULN.
* Known chronic hepatitis B or hepatitis C infection.
* Any other serious medical condition, according to the medical judgment of the physician prior to inclusion in the study.
* Any medical condition that could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction).
* Other malignancies during the previous 5 years with the exception of surgically cured carcinoma in-situ of the cervix and basal cell carcinoma or non-melanoma skin cancer.
* Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule as discussed with the patient before inclusion in the study.