GliomaPhase 2NCT00424554

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

A Phase 2 study testing temozolomide in people with Glioma, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Glioma
What is being tested?: temozolomide
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: No sites listed yet
Study dates: 26 Sep 2006to 16 Feb 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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

Who cannot join

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;

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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).

About this study

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.

Conditions: Glioma
Being tested: temozolomide
Medical subject headings: Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

temozolomideDrug
Also called SCH 052365
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.

Study groups in NCT00424554
Study group	Role	What they receive
Temozolomide treatment	Experimental	Not described Receives: Drug: temozolomide
No treatment	No intervention	Not described

What is being measured

The primary outcome is the main question the study is designed to answer.

MethylGuanine-DNA MethylTransferase [MGMT] Activity Measured From the Tumor Tissue During Surgery
An experimental assay was developed to measure MGMT levels.
Measured: 14 days

Secondary outcomes (4)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 14 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Sep 200616 Feb 2011

First posted19 Jan 2007 (estimated)
Study start26 Sep 2006
Primary completion11 Jan 2010
Study completion16 Feb 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for GliomaStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00424554
Sponsor's protocol ID: P04602
Status last verified: May 2017
First submitted: 18 Jan 2007
Last updated: 7 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: 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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 2/3
A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma
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Active, not recruitingPhase 1/2
RNA Lipid Particles Targeting Pediatric Recurrent Intracranial Malignancies and Other systEmic Solid Tumors
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Adoptive T Cell Therapy, DC Vaccines, and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade in Patients With Medulloblastoma
Recurrent Group 3 Medulloblastoma, Recurrent Group 4 (Non-SHH/Non-WNT) Medulloblastoma
Not yet recruiting
Safety and Efficacy of Autologous Natural Killer Cell Therapy (CHANK-101) in Patients With Recurrent Glioblastoma
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RecruitingEarly Phase 1
Pilot Study of IT Topotecan and Maintenance Chemotherapy for HR-EBTs in Children < 6 Years, Post Consolidation
CNS Embryonal Tumor, CNS, Medulloblastoma

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Study at a glance

From the registry record, last updated by the sponsor on 7 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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.
ClinicalTrials.gov ID: NCT00424554
Acronym / sponsor ID: P04602
Conditions: Glioma
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 26 Sep 2006 (actual)
Primary completion: 11 Jan 2010 (actual)
Study completion: 16 Feb 2011 (actual)
First posted: 19 Jan 2007 (estimated)
Results: Posted 29 Jun 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Temozolomide treatment	Experimental	Drug: temozolomide
No treatment	No intervention	–

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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.

Key exclusion criteria (15 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
temozolomideAlso: SCH 052365Temozolomide 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.	Drug	Temozolomide treatment

Primary outcome

MethylGuanine-DNA MethylTransferase [MGMT] Activity Measured From the Tumor Tissue During Surgery
Time frame: 14 days
An experimental assay was developed to measure MGMT levels.

4 secondary outcomes

Safety: Number of Participants Who Experienced Grade 3 or 4 Toxicities
Time frame: 12 months
Tolerability: Number of Participants Discontinuing Treatment Due to Adverse Events (AE)
Time frame: 12 months
Concentrations of Temozolomide in the Serum, Cerebrospinal Fluid, and Brain Tumor
Time frame: 14 days
MGMT Activity in the Brain Tumor Tissues by Temozolomide Levels
Time frame: 14 days

Results and safety

Results posted to the registry on 29 Jun 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Temozolomide (TMZ)	34	34
No Intervention	6	6

Primary outcome: MethylGuanine-DNA MethylTransferase [MGMT] Activity Measured From the Tumor Tissue During Surgery

Time frame: 14 days. Mean (Standard Deviation). Unit: fmol/mg of proteins

Measure	Temozolomide (TMZ) n = 33	No Intervention n = 5
Value	333.7 (288.5)	105.1 (155)

Temozolomide (TMZ) vs No Intervention: p = 0.09, t-test, 2 sided

Population analysed: All participants for which a MGMT activity assay could be performed

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Temozolomide	0 of 34 (0%)	13 of 34 (38.2%)	Not reported
No Intervention	0 of 6 (0%)	5 of 6 (83.3%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. 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

Related trials for Glioma

RecruitingPhase 2/3
A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma
Glioblastoma
Active, not recruitingPhase 1/2
RNA Lipid Particles Targeting Pediatric Recurrent Intracranial Malignancies and Other systEmic Solid Tumors
Recurrent Pulmonary Osteosarcoma, Recurrent High-grade Glioma
RecruitingPhase 1
Adoptive T Cell Therapy, DC Vaccines, and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade in Patients With Medulloblastoma
Recurrent Group 3 Medulloblastoma, Recurrent Group 4 (Non-SHH/Non-WNT) Medulloblastoma
Not yet recruiting
Safety and Efficacy of Autologous Natural Killer Cell Therapy (CHANK-101) in Patients With Recurrent Glioblastoma
Recurrent Glioblastoma
RecruitingEarly Phase 1
Pilot Study of IT Topotecan and Maintenance Chemotherapy for HR-EBTs in Children < 6 Years, Post Consolidation
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing temozolomide in people with Glioma, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MethylGuanine-DNA MethylTransferase [MGMT] Activity Measured From the Tumor Tissue During Surgery (time frame: 14 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00424554.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2017.