The Feasibility and Efficacy of Dose Timing (Morning vs Evening) of Temozolomide in the Treatment of Glioblastoma

NCT ID: NCT06850766

Last Updated: 2025-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-08

Study Completion Date

2031-05-31

Brief Summary

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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. Participants will wear a wrist actigraphy device for the first cycle of TMZ. 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, biological timing of TMZ delivery, and changes in condition over time. This pilot study will help investigators plan for a larger, pragmatic randomized clinical trial in the future.

Detailed Description

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TMZ-CHRONO is a randomized, multi-centre pilot trial evaluating the feasibility of chronotherapy (dose-timing) for temozolomide (TMZ) in IDH-wildtype glioblastoma (GBM).

The body's biological functions follow a circadian rhythm. Chronotherapy is the deliberate timing of medications to enhance therapeutic benefit and/or minimize toxicity, and can be achieved by dose-timing treatments. There is evidence suggesting that cancer cells may react differently to chemotherapy 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. TMZ is a standard of care treatment for GBM, however there is currently no consensus or guideline with respect to the optimal timing of adjuvant TMZ administration. The study team recently conducted systematic review on TMZ chronotherapy in the treatment of glioma. With emerging evidence that TMZ timing may be important, it is paramount to conduct a large pragmatic randomized study to assess this claim in GBM. The current study is a minimal risk pilot trial to inform the development of a larger, pragmatic randomized clinical trial in the future.

Prospective participants will be approached by their physician (or a member within the circle of care) during their routine clinic visit to begin the integrated verbal consent model process. The physician will explain that the patient is receiving standard of care treatment, with the only change being the timing of adjuvant TMZ (morning vs evening). The physician will then ask the patient for verbal consent to participate in this research study and document this consent in the patient's electronic medical record. Eligible and consenting patients will be randomized to one of two study arms (morning administration of TMZ, and evening administration of TMZ) in a 1:1 fashion using a permuted block design through the Ottawa Methods Centre. Randomization will be stratified by cancer centre \[The Ottawa Hospital Cancer Centre (TOHCC) and the London Health Sciences Centre (LHSC); Canada\]. The participants and investigators will not be blinded to treatment arm allocations. The participants will wear a wrist actigraphy device during the first cycle of TMZ.

The primary aim of the study is to understand if taking TMZ at a prescribed time of day (morning/evening) is feasible in adults with GBM. The secondary aims of the study are to evaluate participant recruitment, safety, health-related quality of life, biological timing of TMZ deliver, and changes in condition over time. Data is collected throughout the study at baseline, randomization, pre/post-TMZ cycles, and at 4-, 8-, 12-, 24-, and 48-weeks after baseline. The study team will continue to follow the participant conditions after TMZ completion for up to 5 years.

This pilot trial is the first and necessary step to assess the feasibility of randomized treatment allocation, rate of pill diary completion, and metrics surrounding participant accrual. This will help determine the number of recruitment sites and expected duration of accrual for a future pragmatic, randomized clinical trial on chronotherapy of TMZ in IDH-wildtype GBM.

Conditions

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IDH-Wildtype Glioblastoma Glioblastoma (GBM)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Pragmatic pilot/feasibility trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Participants and investigators will not be blinded to treatment arm allocations due to the lack of placebo pills for TMZ in this study. The study aims to answer clinical questions using a pragmatic clinical trial design.

Study Groups

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Morning administration of TMZ

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

Group Type ACTIVE_COMPARATOR

Morning administration of TMZ

Intervention Type OTHER

Administration of TMZ within 2 hours of waking

Evening administration of TMZ

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

Group Type ACTIVE_COMPARATOR

Evening administration of TMZ

Intervention Type OTHER

Administration of TMZ within 2 hours of bedtime

Interventions

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Morning administration of TMZ

Administration of TMZ within 2 hours of waking

Intervention Type OTHER

Evening administration of TMZ

Administration of TMZ within 2 hours of bedtime

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 18 years of age or older
* Newly diagnosed IDH-wildtype glioblastoma
* Completed maximal safe brain tumor resection
* Completed post-operative brain RT
* Plan to proceed with up to 6 cycles of adjuvant TMZ within 8 weeks of completing post-operative RT
* Able and willing to provide oral informed consent

Exclusion Criteria

* Unable or unwilling to complete study questionnaires
* Metastatic or incurable cancer other than IDH-wild type glioblastoma
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Ottawa Hospital

OTHER

Sponsor Role collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Terry Ng, MD

Role: PRINCIPAL_INVESTIGATOR

The Ottawa Hospital Cancer Centre

Locations

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London Health Sciences Centre

London, Ontario, Canada

Site Status RECRUITING

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Lisa Vandermeer, MSc

Role: CONTACT

613-737-7700

Lauren Butterfield, MSc

Role: CONTACT

613-737-7700 ext. 75727

Facility Contacts

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Seth Climans, MD

Role: primary

519-685-8600

Lisa Vandermeer, MSc

Role: primary

613-737-7700

References

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Jia JL, Alshamsan B, Ng TL. Temozolomide Chronotherapy in Glioma: A Systematic Review. Curr Oncol. 2023 Feb 4;30(2):1893-1902. doi: 10.3390/curroncol30020147.

Reference Type BACKGROUND
PMID: 36826108 (View on PubMed)

Related Links

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https://react.ohri.ca/

The Rethinking Clinical Trials (REaCT) website

Other Identifiers

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TMZ-CHRONO

Identifier Type: -

Identifier Source: org_study_id

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