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

NCT06850766 | Recruiting

• 1 other identifier: TMZ-CHRONO
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

IDH-Wildtype Glioblastoma; Glioblastoma (GBM)

Keywords

temozolomide; chronotherapy; dose timing; cancer; oncology; glioblastoma; chemotherapy

Outcome Measures

Primary Outcomes (1)

• Feasibility: adherence to TMZ dose timing protocol

  The primary outcome is feasibility for patients to receive temozolomide (TMZ) according to their assigned dose timing. Feasibility is measured by at least 80% adherence to the assigned TMZ dose timing. Adherence is calculated based on patient entries in a daily pill diary.

  Patients complete daily pill diaries on days 1-5 of a 28-day cycle for up to 6 cycles. It is expected that the first cycle will begin within 8 weeks of the last fraction (dose) of radiation. Adherence is calculated at Week 48.

Secondary Outcomes (16)

• Participant recruitment: proportion of patients providing consent to participate

  The number of patients providing consent to participate will be collected during the recruitment period and the total number/proportion will be calculated upon completion of recruitment. The anticipated recruitment period length is one year.

• Participant recruitment: participant withdrawal rate and reasons

  Withdrawal rate and reasons will be collected from enrollment to start of adjuvant TMZ

• Participant recruitment: rate of patient enrollment

  The number of patients enrolled in the study will be collected during the recruitment period. The anticipated recruitment period is one year.

• Safety: rate of hospital admissions

  The number of hospitalizations will be collected from the start of adjuvant TMZ until 6 weeks after the last TMZ cycle (28-day cycles for up to 6 cycles). The number of hospitalizations per participant will be calculated at Week 48.

• Safety: number of TMZ cycles

  The number of TMZ cycles will be calculated at Week 48, once all questionnaires and adjuvant treatment cycles are complete.

Study Arms (2)

Morning administration of TMZ

ACTIVE COMPARATOR

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

Other: Morning administration of TMZ

Evening administration of TMZ

ACTIVE COMPARATOR

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

Other: Evening administration of TMZ

Interventions

Morning administration of TMZ OTHER

Administration of TMZ within 2 hours of waking

Morning administration of TMZ

Evening administration of TMZ OTHER

Administration of TMZ within 2 hours of bedtime

Evening administration of TMZ

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Unable or unwilling to complete study questionnaires
• Metastatic or incurable cancer other than IDH-wild type glioblastoma

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• The Ottawa Hospital: collaborator

Study Sites (2)

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

RECRUITING

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Related Publications (1)

• 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.

  PMID: 36826108 BACKGROUND

Related Links

• The Rethinking Clinical Trials (REaCT) website

MeSH Terms

Conditions

Glioblastoma; Neoplasms

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Terry Ng, MD

  The Ottawa Hospital Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa Vandermeer, MSc

CONTACT

613-737-7700; lvandermeer@ohri.ca

Lauren Butterfield, MSc

CONTACT

613-737-7700; lbutterfield@ohri.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pragmatic pilot/feasibility trial.

Study Record Dates

• First Submitted: February 5, 2025
• First Posted: February 27, 2025
• Study Start: May 8, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): May 1, 2031
• Last Updated: April 2, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)