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Trial Title:
Investigating Mechanistic Predictors of Interpatient Variability and Temozolomide (TMZ) Induced Haematological Toxicity for Glioma Patients
NCT ID:
NCT06546631
Condition:
Glioma
Conditions: Official terms:
Glioma
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
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 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.
Criteria for eligibility:
Study pop:
Patients under the care of a medical oncologist attending a hospital clinic for the
treatment of their high grade glioma
Sampling method:
Non-Probability Sample
Criteria:
Part A
Inclusion Criteria:
1. 18 years of age or over
2. 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).
3. Provision of informed consent to participate.
Exclusion Criteria:
a. 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
Inclusion Criteria:
1. 18 years of age or over
2. Receiving or received treatment with TMZ for high grade glioma (WHO Grade 3 or Grade
4 Astrocytoma, Oligodendroglioma or Glioblastoma).
3. Developed any CTCAE Grade ≥3 Haematological Toxicity associated with Temozolomide,
and/or any 1 of:
i. 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.
d. Provision of informed consent to participate.
Exclusion criteria:
a. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Locations:
Facility:
Name:
Cork University Hospital
Address:
City:
Cork
Country:
Ireland
Status:
Recruiting
Start date:
August 22, 2024
Completion date:
February 2027
Lead sponsor:
Agency:
University College Cork
Agency class:
Other
Collaborator:
Agency:
University Hospital Waterford
Agency class:
Other
Source:
University College Cork
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06546631
