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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Temozolomide treatment | Experimental |
| |
| No treatment | No Intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| 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 |
| 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) |
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Inclusion Criteria:
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):
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | Temozolomide (TMZ) | Temozolomide 75 mg/m^2 daily for 14 days prior to surgery. As standard of care, it could also have been given at the same dose for up to 28 days after surgery, per investigator discretion. |
| FG001 | No Intervention | No pre-surgery treatment with temozolomide |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Temozolomide (TMZ) | Temozolomide 75 mg/m^2 daily for 14 days prior to surgery. As standard of care, it could also have been given at the same dose for up to 28 days after surgery, per investigator discretion. |
| BG001 | No Intervention |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Age range: 18-75 years |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | MethylGuanine-DNA MethylTransferase [MGMT] Activity Measured From the Tumor Tissue During Surgery | An experimental assay was developed to measure MGMT levels. | All participants for which a MGMT activity assay could be performed | Posted | Mean | Standard Deviation | fmol/mg of proteins | 14 days |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Temozolomide | Temozolomide 75 mg/m^2 daily for 14 days prior to surgery. As standard of care, it could also have been given at the same dose for up to 28 days after surgery, per investigator discretion. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| LYMPHOPENIA | Blood and lymphatic system disorders | MedDRA 12.1 | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D005910 | Glioma |
| ID | Term |
|---|---|
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
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|
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 |
No pre-surgery treatment with temozolomide |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
|
| Secondary | 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. | Posted | Number | participants | 12 months |
|
|
|
| Secondary | 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. | Posted | Number | participants | 12 months |
|
|
|
| Secondary | 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. | Posted | 14 days |
|
|
| Secondary | 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. | Posted | 14 days |
|
|
| 0 |
| 34 |
| 13 |
| 34 |
| EG001 | No Intervention | No pre-surgery treatment with temozolomide | 0 | 6 | 5 | 6 |
| THROMBOCYTOPENIA | Blood and lymphatic system disorders | MedDRA 12.1 | Systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| PAIN | General disorders | MedDRA 12.1 | Systematic Assessment |
|
| URINARY TRACT INFECTION | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
|
| POSTOPERATIVE FEVER | Injury, poisoning and procedural complications | MedDRA 12.1 | Systematic Assessment |
|
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA 12.1 | Systematic Assessment |
|
| HYPERGLYCAEMIA | Metabolism and nutrition disorders | MedDRA 12.1 | Systematic Assessment |
|
| HYPOKALAEMIA | Metabolism and nutrition disorders | MedDRA 12.1 | Systematic Assessment |
|
| HYPONATRAEMIA | Metabolism and nutrition disorders | MedDRA 12.1 | Systematic Assessment |
|
| MUSCULAR WEAKNESS | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| COMPLEX PARTIAL SEIZURES | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| CONVULSION | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| HEMIPARESIS | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| SPEECH DISORDER | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| VISUAL FIELD DEFECT | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
|
| HYPOXIA | Respiratory, thoracic and mediastinal disorders | MedDRA 12.1 | Systematic Assessment |
|
| RASH | Skin and subcutaneous tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| SKIN IRRITATION | Skin and subcutaneous tissue disorders | MedDRA 12.1 | Systematic Assessment |
|
| THROMBOSIS | Vascular disorders | MedDRA 12.1 | Systematic Assessment |
|
The principal investigator (PI) agrees not to publish or publicly present any interim results of the Study without prior written consent of the sponsor. The PI further agrees to provide 45 days written notice to the sponsor prior to submission for publication or presentation to permit the sponsor to review, without limitation, including editorial rights. If the parties disagree, the PI agrees to meet with the sponsor to discuss and resolve any such issues or disagreement.
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |