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 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).
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.