Clinical trial NCT00424554: Low-dose Temozolomide for 2 Weeks on Brain Tumor Enzyme in Patients With Gliomas (P04602 AM1) (Completed)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2007-01-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: MethylGuanine-DNA MethylTransferase [MGMT] Activity Measured From the Tumor Tissue During Surgery
timeFrame: 14 days
Secondary outcomes:
measure: Safety: Number of Participants Who Experienced Grade 3 or 4 Toxicities
timeFrame: 12 months
measure: Tolerability: Number of Participants Discontinuing Treatment Due to Adverse Events (AE)
timeFrame: 12 months
measure: Concentrations of Temozolomide in the Serum, Cerebrospinal Fluid, and Brain Tumor
timeFrame: 14 days
measure: MGMT Activity in the Brain Tumor Tissues by Temozolomide Levels
timeFrame: 14 days
Other outcomes:
Locations:
Study officials:
References: