GliomaImprove TMZNCT06546631
Investigating Mechanistic Predictors of Interpatient Variability and Temozolomide (TMZ) Induced Haematological Toxicity for Glioma Patients
An observational study of Glioma, run by University College Cork at 1 site in Ireland.
Trial summary
A medication called temozolomide has been used for many years in the treatment of high-grade gliomas, which are tumours that originate in the brain. While this drug is the normal treatment for high-grade glioma, a number of patients develop a side-effect which results in low levels of some important blood cells, such… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma
- How many people
- 55 participants
- Where
- 1 siteIreland
- Study dates
- 22 Aug 2024to Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- Adult, Older adult
Study population: Patients under the care of a medical oncologist attending a hospital clinic for the treatment of their high grade glioma
Who may be able to join
- 18 years of age or over
- Will receive or are currently receiving concurrent phase treatment with TMZ for high grade glioma (WHO Grade 3 or Grade 4 Astrocytoma, Oligodendroglioma or Glioblastoma).
- Provision of informed consent to participate.
- 18 years of age or over
- Receiving or received treatment with TMZ for high grade glioma (WHO Grade 3 or Grade 4 Astrocytoma, Oligodendroglioma or Glioblastoma).
- Developed any CTCAE Grade ≥3 Haematological Toxicity associated with Temozolomide, and/or any 1 of:
- Platelet count <100 x 109/L ii. Neutrophil Count <1.0 x 109/L iii. Haemoglobin value <8.0 g/L iv. Omission of daily TMZ dose for ≥3 consecutive days during concurrent phase due to FBC concerns v. Deferral of subsequently due TMZ cycle by ≥7 days during adjuvant phase; vi. Dose reduction or permanent discontinuation of TMZ for reasons of haematological toxicity (as per treating physician discretion); vii. Use of growth factors, platelets or packed-cell transfusions during the course of TMZ.
- Provision of informed consent to participate.
Who cannot join
- Patients who, in opinion of supervising clinician, are clinically too unwell to provide informed consent or for whom additional blood samples, or other research samples, would not be indicated or appropriate.
- Part B
- Patients who, in opinion of supervising clinician, are clinically too unwell to provide informed consent or for whom additional blood samples, or other research samples, would not be indicated or appropriate.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
A medication called temozolomide has been used for many years in the treatment of high-grade gliomas, which are tumours that originate in the brain. While this drug is the normal treatment for high-grade glioma, a number of patients develop a side-effect which results in low levels of some important blood cells, such as platelets or white blood cells. If this side-effect occurs, treatment with temozolomide may have to be stopped or paused, which may affect how well this treatment works.
At present, it is unknown why some patients develop this side effect and others do not. It is known that patients with a higher concentration of temozolomide in their blood are at an increased risk of developing this toxicity. There may be some factors associated with the movement of the drug in the body or the removal of the drug from the body which may affect the concentration of temozolomide in blood. There are many factors which may be involved, including genes, other medicines that are taken, how well kidneys and liver are working or even the microbiome (which is the bacteria in the gut).
This study is being done to find out what these factors could be. In the future, this may lead to medical care teams being able to predict which patients are at higher risk of side-effects, allowing them to implement measures to reduce the risk of this occurring.
Read the detailed description
Concurrent (with radiotherapy) and adjuvant temozolomide (TMZ) is the standard of care treatment for high grade glioma, however, severe haematological toxicity is a major dose limiting factor, impacting 16-45% of patients in different studies. The investigators hypothesize that mechanistic factors such as genetic polymorphisms, renal function or other patient factors such as sex, concomitant medications or the microbiome result in this interpatient variability in toxicity. This study aims to develop a pharmacokinetic model of temozolomide to test the effect of these potential covariates on TMZ concentration (Part A) in patients with brain tumours being treated with TMZ. Using this model, the investigators aim to assess patients who develop haematological toxicity from TMZ for mechanistic predictors of this toxicity (Part B).
The investigators hypothesise that the development of severe TMZ-induced haematological toxicity is due to higher exposure to temozolomide in plasma, driven by mechanistic factors, such as pharmacogenomic variants, the microbiome or demographic factors.
- Conditions
- Glioma
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Temozolamide treatment | Patients who are being started on Temozolamide treatment for high-grade glioma. Patients will provide blood, saliva and stool samples. | |
| Temozolamide toxicity | Patients who have developed dose-limiting haematological toxicity during treatment with TMZ for a high grade glioma. Patients will provide blood, saliva and stool samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine potential predisposing factors for severe haematological toxicity from temozolamide
Analysis of pharmacogenes
Measured: On study registration
Determine potential predisposing factors for severe haematological toxicity from temozolamide
Microbiome analysis of stool bacterial composition
Measured: Baseline and study completion, an average of 9 months
Secondary outcomes (8)
Assess duration of haematological toxicity from temozolamide
Duration measured in time (days/weeks).
Measured: Up to 12 months
Assess severity of haematological toxicity from temozolamide
Severity measured by Common Terminology Criteria for Adverse Events (CTCAE) Grade (grades range from 1-5, with higher grades indicating higher severity).
Measured: Up to 12 months
Assess the impact of haematological toxicity on patients
Number of blood transfusions required as a result of the haematological toxicity
Measured: Up to 12 months
Assess the impact of haematological toxicity on patients
Number of platelet transfusions required as a result of the haematological toxicity
Measured: Up to 12 months
Assess the impact of toxicity on patients distress tool scores
The European Organisation for Research and Treatment of Cancer (EoRTC) Quality of Life questionnaires for cancer patients (C-30, scores range from 30-126). Higher scores indicate lower quality of life.
Measured: On date of study registration
Assess the impact of toxicity on patients quality of life scores
The European Organisation for Research and Treatment of Cancer (EoRTC) Quality of Life questionnaires for cancer patients brain-specific module BN-20 (scores range from 20-80). Higher scores indicate lower quality of life.
Measured: On date of study registration
Assess the impact of toxicity on patients distress tool scores
The National Comprehensive Cancer Network distress thermometer (scores range from 0-10). Higher scores indicate more extreme distress.
Measured: On date of study registration
Overall survival
Overall survival
Measured: From date of study registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2024
- Study start22 Aug 2024
- Primary completionJul 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliomaStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College Cork
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Waterford
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06546631
- Sponsor's protocol ID
- 24010
- Acronym
- Improve TMZ
- Status last verified
- Mar 2026
- First submitted
- 29 Jul 2024
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Mechanistic Predictors of Interpatient Variability and Temozolomide (TMZ) Induced Haematological Toxicity for Glioma Patients
- ClinicalTrials.gov ID
- NCT06546631
- Acronym / sponsor ID
- Improve TMZ / 24010
- Conditions
- Glioma
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- University College CorkUniversity, hospital or other
- Collaborators
- University Hospital Waterford
- Study start
- 22 Aug 2024 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 9 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A medication called temozolomide has been used for many years in the treatment of high-grade gliomas, which are tumours that originate in the brain. While this drug is the normal treatment for high-grade glioma, a number of patients develop a side-effect which results in low levels of some important blood cells, such as platelets or white blood cells. If this side-effect occurs, treatment with temozolomide may have to be stopped or paused, which may affect how well this treatment works.
At present, it is unknown why some patients develop this side effect and others do not. It is known that patients with a higher concentration of temozolomide in their blood are at an increased risk of developing this toxicity. There may be some factors associated with the movement of the drug in the body or the removal of the drug from the body which may affect the concentration of temozolomide in blood. There are many factors which may be involved, including genes, other medicines that are taken, how well kidneys and liver are working or even the microbiome (which is the bacteria in the gut).
This study is being done to find out what these factors could be. In the future, this may lead to medical care teams being able to predict which patients are at higher risk of side-effects, allowing them to implement measures to reduce the risk of this occurring.
Detailed description
Concurrent (with radiotherapy) and adjuvant temozolomide (TMZ) is the standard of care treatment for high grade glioma, however, severe haematological toxicity is a major dose limiting factor, impacting 16-45% of patients in different studies. The investigators hypothesize that mechanistic factors such as genetic polymorphisms, renal function or other patient factors such as sex, concomitant medications or the microbiome result in this interpatient variability in toxicity. This study aims to develop a pharmacokinetic model of temozolomide to test the effect of these potential covariates on TMZ concentration (Part A) in patients with brain tumours being treated with TMZ. Using this model, the investigators aim to assess patients who develop haematological toxicity from TMZ for mechanistic predictors of this toxicity (Part B).
The investigators hypothesise that the development of severe TMZ-induced haematological toxicity is due to higher exposure to temozolomide in plasma, driven by mechanistic factors, such as pharmacogenomic variants, the microbiome or demographic factors.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Temozolamide treatment | – | –Patients who are being started on Temozolamide treatment for high-grade glioma. Patients will provide blood, saliva and stool samples. |
| Temozolamide toxicity | – | –Patients who have developed dose-limiting haematological toxicity during treatment with TMZ for a high grade glioma. Patients will provide blood, saliva and stool samples |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients under the care of a medical oncologist attending a hospital clinic for the treatment of their high grade glioma
Key inclusion criteria (8 listed)
- 18 years of age or over
- Will receive or are currently receiving concurrent phase treatment with TMZ for high grade glioma (WHO Grade 3 or Grade 4 Astrocytoma, Oligodendroglioma or Glioblastoma).
- Provision of informed consent to participate.
- 18 years of age or over
- Receiving or received treatment with TMZ for high grade glioma (WHO Grade 3 or Grade 4 Astrocytoma, Oligodendroglioma or Glioblastoma).
Key exclusion criteria (3 listed)
- Patients who, in opinion of supervising clinician, are clinically too unwell to provide informed consent or for whom additional blood samples, or other research samples, would not be indicated or appropriate.
- Part B
- Patients who, in opinion of supervising clinician, are clinically too unwell to provide informed consent or for whom additional blood samples, or other research samples, would not be indicated or appropriate.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Determine potential predisposing factors for severe haematological toxicity from temozolamide
Time frame: On study registration
Analysis of pharmacogenes
Determine potential predisposing factors for severe haematological toxicity from temozolamide
Time frame: Baseline and study completion, an average of 9 months
Microbiome analysis of stool bacterial composition
8 secondary outcomes
Assess duration of haematological toxicity from temozolamide
Time frame: Up to 12 months
Assess severity of haematological toxicity from temozolamide
Time frame: Up to 12 months
Assess the impact of haematological toxicity on patients
Time frame: Up to 12 months
Assess the impact of haematological toxicity on patients
Time frame: Up to 12 months
Assess the impact of toxicity on patients distress tool scores
Time frame: On date of study registration
Assess the impact of toxicity on patients quality of life scores
Time frame: On date of study registration
Assess the impact of toxicity on patients distress tool scores
Time frame: On date of study registration
Overall survival
Time frame: From date of study registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2026.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Glioma, run by University College Cork at 1 site in Ireland.
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 8 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jack Gleeson (0214922603, jgleeson@ucc.ie), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine potential predisposing factors for severe haematological toxicity from temozolamide (time frame: On study registration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Mar 2026.