Low-dose Temozolomide for 2 Weeks on Brain Tumor Enzyme in Patients With Gliomas (P04602 AM1) (Completed)

A Phase II Trial to Evaluate the Effect of Low Dose Temozolomide (TMZ) for 2 Weeks on Brain Tumor O-6-methylguanine-DNA Methyltransferase (MGMT) Activity in Patients With Gliomas.

The main purpose of this study is to assess the effect of a two-week pre-surgery treatment with low-dose temozolomide (TMZ) on brain tumor methylguanine-DNA (deoxyribonucleic acid) methyltransferase (MGMT) activity in patients with gliomas.

Inclusion Criteria:

• Presence of a brain tumor with high probability of being a glioma as detected by Magnetic Resonance Imaging (MRI). These would include newly diagnosed tumors or potentially recurrent gliomas.
• No prior treatment for the tumor including chemotherapy or radiotherapy.
• Amenable to surgery for biopsy or resection of the brain tumor. Surgically confirmed diagnosis of glioma (glioblastoma multiforme [GBM], anaplastic astrocytoma [AA], anaplastic oligodendroglioma [AO], anaplastic oligoastrocytoma [AOA], astrocytoma [A] or oligodendroglioma [O]) will be

required for patients to be maintained in the study. Those not fulfilling this requirement will be discontinued and will be replaced.

• Use of medically approved contraception in fertile males and females.
• Women with childbearing potential must have a negative urine or serum

pregnancy test (urinary excretion or serum level of beta-Human Chorionic

Gonadotropin [bHCG]) within 72 hours of randomization.

• Karnofsky Performance Status score >= 70%.
• Signed informed consent form

Exclusion Criteria:

• Prior chemotherapy.

• Prior radiotherapy at the tumor site.

• History of non-compliance to other therapies.

• Inadequate haematological, 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 x 10^9/L;
  • Platelets ≤100 x 10^9/L;
  • Haemoglobin <90 g/L;
  • Serum creatinine ≥1.5 times upper limit of laboratory normal;
  • Total serum bilirubin ≥1.5 times upper limit of laboratory normal (ULN);
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.0 ULN;
  • Alkaline phosphatase of > 2.5 ULN.

• Known Human Immunodeficiency Virus [HIV] infection.

• 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, which could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction).