Temozolomide Timing for Glioblastoma

(TMZ-CHRONO Trial)

Recruiting at 1 trial location

Overseen By Lauren Butterfield, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ottawa Hospital Research Institute

Must be taking: Temozolomide

Disqualifiers: Metastatic cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24-28 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the time of day for taking the chemotherapy pill Temozolomide (TMZ) affects its effectiveness in treating glioblastoma, a type of brain cancer. Participants will be divided into two groups: one takes TMZ in the morning, and the other in the evening. The study aims to determine if this timing approach is practical and safe, while also monitoring changes in quality of life and health over time. Ideal candidates are adults recently diagnosed with glioblastoma who have completed brain surgery and radiation and are ready to start chemotherapy. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could improve treatment strategies for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It focuses on the timing of taking the chemotherapy drug Temozolomide (TMZ).

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research shows that temozolomide (TMZ), a chemotherapy pill, is often used to treat glioblastoma, a type of brain cancer. This medicine is already approved and has been safely used in people before. Studies suggest that taking TMZ in the morning might be more effective and help patients live longer than taking it in the evening. However, morning doses may lead to more side effects, though specific side effects are not detailed in the sources.

Taking TMZ in the evening is linked to fewer side effects. The pill is generally considered safe, having been used for a while to treat glioblastoma. While side effects may vary depending on the timing of the dose, TMZ remains a well-known and commonly used treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for glioblastoma, like standard chemotherapy with temozolomide, focus on attacking cancer cells. However, researchers are excited about this trial because it explores whether the timing of taking temozolomide—either in the morning or evening—can make a difference in effectiveness and side effects. This approach is unique because it considers the body's natural rhythms and how they might affect drug metabolism and cancer cell vulnerability, potentially enhancing treatment outcomes and improving patient quality of life.

What evidence suggests that taking Temozolomide at a specific time of day might be effective for glioblastoma?

This trial will compare the effects of taking temozolomide (TMZ) in the morning versus the evening for patients with glioblastoma. Research has shown that taking TMZ in the morning might extend patient survival. Specifically, studies found that patients who took TMZ in the morning lived, on average, 3.6 months longer than those who took it in the evening, with an average survival of about 17 months after diagnosis. This suggests that the time of day TMZ is taken could influence its effectiveness. Although treating high-grade gliomas remains challenging, taking TMZ in the morning might offer a small advantage. ^{1 2 6 7 8}

Who Is on the Research Team?

Terry Ng, MD

Principal Investigator

The Ottawa Hospital Cancer Centre

Are You a Good Fit for This Trial?

This trial is for adults with glioblastoma who have completed brain surgery and radiation. They must be able to take a chemotherapy pill called Temozolomide (TMZ) and keep a diary of when they take it. The study will exclude certain individuals based on criteria not specified here.

Inclusion Criteria

I have finished treatment for my brain with radiation after surgery.

I've had surgery to remove as much of my brain tumor as safely possible.

Able and willing to provide oral informed consent

Exclusion Criteria

I cannot or do not want to fill out study questionnaires.

My cancer is advanced and cannot be cured, but it's not IDH-wild type glioblastoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to take temozolomide (TMZ) either in the morning or evening for up to 6 cycles, each cycle lasting 28 days

24-28 weeks

Daily self-administration with regular clinic visits

Follow-up

Participants are monitored for safety, health-related quality of life, and overall survival after treatment completion

5 years

Regular follow-up visits and assessments

What Are the Treatments Tested in This Trial?

Interventions

• Temozolomide

Trial Overview The study tests if the time of day TMZ is taken affects its effectiveness in treating glioblastoma. Participants are randomly assigned to take TMZ either in the morning or evening, and their health outcomes are monitored to plan for future larger trials.

How Is the Trial Designed?

Group I: Morning administration of TMZ Active Control 1 Intervention

Participants were instructed to take the prescribed daily dose of temozolomide (TMZ) in the morning.

Group II: Evening administration of TMZ Active Control 1 Intervention

Participants were instructed to take the prescribed daily dose of temozolomide (TMZ) in the evening.

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

The Ottawa Hospital

Collaborator

Trials

97

Recruited

64,000+

Published Research Related to This Trial

In a trial involving 40 glioblastoma patients, the maximum tolerated dose (MTD) of intensity-modulated radiotherapy (IMRT) was determined to be 70 Gy, delivered in 25 fractions, without unacceptable acute toxicity.

The study demonstrated that this high dose of radiation, combined with standard doses of temozolomide (TMZ), did not result in significant late neurological toxicity after a median follow-up of 25 months, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated intensity-modulated radiotherapy plus temozolomide in patients with glioblastoma: a phase I dose-escalation study (ISIDE-BT-1). Massaccesi, M., Ferro, M., Cilla, S., et al.[2022]

In a study of 85 patients with newly diagnosed glioblastoma, the dose-dense regimen of temozolomide resulted in an impressive 1-year survival rate of 80%, compared to 69% for the metronomic regimen, suggesting it may be a more effective treatment option.

Both treatment regimens were well tolerated with manageable side effects, primarily myelosuppression and elevated liver enzymes, indicating that they are safe options for patients undergoing adjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma. Clarke, JL., Iwamoto, FM., Sul, J., et al.[2022]

Temozolomide, a new chemotherapy drug, was tested on 16 patients with recurrent glioblastoma multiforme, showing a median overall survival of 6.5 months and a 1-year survival rate of 16%.

The survival outcomes with temozolomide were comparable to other studies, indicating its potential effectiveness, and suggesting the need for further randomized trials to explore its use in initial treatment and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in second-line treatment after prior nitrosurea-based chemotherapy in glioblastoma multiforme: experience from a Portuguese institution. Teixeira, MM., Garcia, I., Portela, I., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9955138/

Temozolomide Chronotherapy in Glioma: A Systematic Review Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma ...

2. medicine.washu.edu medicine.washu.edu/news/chemo-for-glioblastoma-may-work-better-in-morning-than-evening/

Chemo for glioblastoma may work better in morning than ... Those receiving the chemotherapy drug temozolomide in the morning had an average overall survival of about 17 months post diagnosis, compared with an average ...

3. academic.oup.com academic.oup.com/nop/article/12/2/291/7959516

Temozolomide chemotherapy for patients with newly ... Temozolomide chemotherapy in glioblastoma may be more effective when administered in the morning rather than the evening.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9113320/

A randomized feasibility study evaluating temozolomide ... Our recent retrospective study revealed a 3.6-month longer survival in GBM patients who took TMZ in the morning compared to evening and a 6-month extension of ...

5. trials.braintumor.org trials.braintumor.org/trials/NCT06850766

The Feasibility and Efficacy of Dose Timing (Morning vs ... The primary goal of the study is to understand if taking TMZ at a prescribed time of day (morning/evening) is feasible in adults with glioblastoma.

6. mdpi.com mdpi.com/1718-7729/30/2/147

Temozolomide Chronotherapy in Glioma: A Systematic ... Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT229761

Randomized feasibility study of temozolomide ... Our preliminary data indicate that TMZ chronotherapy is feasible. In addition, AM dosing was associated with higher incidence of adverse events (AE), ...

8. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/579281

The Feasibility and Efficacy of Dose Timing (Morning vs ... The primary goal of the study is to understand if taking TMZ at a prescribed time of day (morning/evening) is feasible in adults with ...