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

NCT00424554 | Completed Phase 2 Results

• 1 other identifier: P04602
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Glioma

Outcome Measures

Primary Outcomes (1)

• MethylGuanine-DNA MethylTransferase [MGMT] Activity Measured From the Tumor Tissue During Surgery

  An experimental assay was developed to measure MGMT levels.

  14 days

Secondary Outcomes (4)

• Safety: Number of Participants Who Experienced Grade 3 or 4 Toxicities

  12 months

• Tolerability: Number of Participants Discontinuing Treatment Due to Adverse Events (AE)

  12 months

• Concentrations of Temozolomide in the Serum, Cerebrospinal Fluid, and Brain Tumor

  14 days

• MGMT Activity in the Brain Tumor Tissues by Temozolomide Levels

  14 days

Study Arms (2)

Temozolomide treatment

EXPERIMENTAL

Drug: temozolomide

No treatment

NO INTERVENTION

Interventions

temozolomide DRUG

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.

Also known as: SCH 052365

Temozolomide treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Prior chemotherapy.
• Prior radiotherapy at the tumor site.
• History of non-compliance to other therapies.
• 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 medical condition, which could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction).

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Glioma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The assay developed to measure MGMT activity had high variability. The TMZ assay was unable to detect the low levels of the drug due to the relatively low dose and short half life of TMZ.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2007
• First Posted: January 19, 2007
• Study Start: September 26, 2006
• Primary Completion: January 11, 2010
• Study Completion: February 16, 2011
• Last Updated: June 7, 2017
• Results First Posted: June 29, 2011

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share