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 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, and changes in
condition over time. Data is collected throughout the study at baseline, randomization,
pre/post-TMZ cycles, and at 4-, 8-, 12-, and 24-weeks following randomization. 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.