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.

Study Overview

• Status: Completed
• Conditions: Glioma
• Intervention / Treatment: Drug: temozolomide

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No treatment
Experimental: Temozolomide treatment	Drug: temozolomide; 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.; Other Names: SCH 052365

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2006
• Primary Completion (Actual): January 11, 2010
• Study Completion (Actual): February 16, 2011

Study Registration Dates

• First Submitted: January 18, 2007
• First Submitted That Met QC Criteria: January 18, 2007
• First Posted (Estimate): January 19, 2007

Study Record Updates

• Last Update Posted (Actual): June 7, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: P04602

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php