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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Glioma

Intervention / Treatment
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* Drug: temozolomide


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temozolomide treatment<br> | Drug: temozolomide<br>* Temozolomide 75 mg/m^2 daily for 14 days prior to surgery. As standard of care, it could also be given at the same dose for up to 28 days after surgery, per investigator discretion.<br>* Other names: SCH 052365;|
| No Intervention: No treatment<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MethylGuanine-DNA MethylTransferase [MGMT] Activity Measured From the Tumor Tissue During Surgery | An experimental assay was developed to measure MGMT levels. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Number of Participants Who Experienced Grade 3 or 4 Toxicities | Grade 3 was defined as severe per Common Terminology Criteria for Adverse Events (CTCAE). Grade 4 was defined as life-threatening per CTCAE. | 12 months | 
| Tolerability: Number of Participants Discontinuing Treatment Due to Adverse Events (AE) | 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. | 12 months | 
| Concentrations of Temozolomide in the Serum, Cerebrospinal Fluid, and Brain Tumor | No data available: at the time of tumor collection, the temozolomide levels were below the detection limits of the assay. | 14 days | 
| MGMT Activity in the Brain Tumor Tissues by Temozolomide Levels | No data available: at the time of tumor collection, the temozolomide levels were below the detection limits of the assay. | 14 days |