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

Trial Summary

What is the purpose of this trial?

The body's biological functions follow a circadian rhythm, meaning that individual biological functions in the body change over a 24-hour cycle. There is evidence suggesting that the body and cancer cells may react differently to anti-cancer treatment based on the time of day they are exposed. In fact, researchers have already found that giving anti-cancer treatments at a particular time of the day works better in rectal and ovarian cancer. Temozolomide (TMZ) is a chemotherapy pill/capsule commonly given to patients with newly diagnosed glioblastoma after brain surgery and radiation treatment. However, there is no current standard for what time of day TMZ should be taken for the treatment of glioblastoma. In the current study, participants are randomly placed in one of two groups: a morning group and an evening group. Based on this group placement, participants are instructed to either take their TMZ in the morning or in the evening and record the date and time they take their TMZ in a pill diary. 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. This is a pilot trial, and the investigators hypothesize that it will be feasible for glioblastoma patients to take TMZ at the prescribed time of day. The secondary goals of this study are to evaluate participant recruitment, safety, health-related quality of life, and changes in condition over time. This pilot study will help investigators plan for a larger, pragmatic randomized clinical trial in the future.

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).

What data supports the effectiveness of the drug Temozolomide for treating glioblastoma?

Research shows that Temozolomide can help improve survival rates and stabilize the disease in patients with glioblastoma. In various studies, patients treated with Temozolomide had improved survival times and better quality of life, with some experiencing stable disease or partial responses. ^{1 2 3 4 5}

Is temozolomide generally safe for humans?

Temozolomide has been studied in various dosing regimens for glioblastoma, and these studies have evaluated its safety. Research indicates that different schedules of temozolomide, such as 7-day on/7-day off and 3-day on/11-day off, have been assessed for safety in patients with glioblastoma, suggesting it is generally safe for use in humans. ^{3 6 7 8 9}

How does the drug Temozolomide differ from other treatments for glioblastoma?

Temozolomide is unique because it is an oral chemotherapy drug that can be used in various dosing schedules, such as a 'one week on/one week off' regimen, which may offer flexibility and potentially improve outcomes for patients with glioblastoma. It is also considered a viable option for elderly patients who may not tolerate traditional radiotherapy well. ^{2 3 10 11 12}

Research Team

Terry Ng, MD

Principal Investigator

The Ottawa Hospital Cancer Centre

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Temozolomide in second-line treatment after prior nitrosurea-based chemotherapy in glioblastoma multiforme: experience from a Portuguese institution. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

One week on/one week off: a novel active regimen of temozolomide for recurrent glioblastoma. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Temozolomide as first-line agent in treating high-grade gliomas: phase II study. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Extended adjuvant temozolomide in newly diagnosed glioblastoma: A single-center retrospective study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Retrospective analysis of safety and feasibility of a 3 days on/11 days off temozolomide dosing regimen in recurrent adult malignant gliomas. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Standard (60 Gy) or short-course (40 Gy) irradiation plus concomitant and adjuvant temozolomide for elderly patients with glioblastoma: a propensity-matched analysis. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

Accelerated intensity-modulated radiotherapy plus temozolomide in patients with glioblastoma: a phase I dose-escalation study (ISIDE-BT-1). [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Phase II study of temozolomide without radiotherapy in newly diagnosed glioblastoma multiforme in an elderly populations. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Temozolomide in glioblastoma: results of administration at first relapse and in newly diagnosed cases. Is still proposable an alternative schedule to concomitant protocol? [2022]

12. United States pubmed.ncbi.nlm.nih.gov

A pilot study of primary temozolomide chemotherapy and deferred radiotherapy in elderly patients with glioblastoma. [2018]