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

Phase 2

Completed

Brief Summary: 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.

Recruitment & Eligibility

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.

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

Gonadotropin [bHCG]) within 72 hours of randomization.

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).

Arm && Interventions

Group	Intervention	Description
Temozolomide treatment	temozolomide	-

Primary Outcome Measures

Name	Time	Method
MethylGuanine-DNA MethylTransferase [MGMT] Activity Measured From the Tumor Tissue During Surgery	14 days	An experimental assay was developed to measure MGMT levels.

Secondary Outcome Measures

Name	Time	Method
MGMT Activity in the Brain Tumor Tissues by Temozolomide Levels	14 days	No data available: at the time of tumor collection, the temozolomide levels were below the detection limits of the assay.
Safety: Number of Participants Who Experienced Grade 3 or 4 Toxicities	12 months	Grade 3 was defined as severe per Common Terminology Criteria for Adverse Events (CTCAE). Grade 4 was defined as life-threatening per CTCAE.
Tolerability: Number of Participants Discontinuing Treatment Due to Adverse Events (AE)	12 months	An AE was defined as any event which was adverse, including what were commonly described as adverse or undesirable experiences, adverse events, adverse reactions, side effects, or death due to any cause associated with, or observed in conjunction with the use of a drug, biological product, or device in humans, whether or not considered related to the use of that product. Additionally, any event which was associated with, or observed in conjunction with product overdose whether accidental or intentional, or product abuse and/or withdrawal was also considered an AE.
Concentrations of Temozolomide in the Serum, Cerebrospinal Fluid, and Brain Tumor	14 days	No data available: at the time of tumor collection, the temozolomide levels were below the detection limits of the assay.