A Randomized, Multicentre Pilot Trial Evaluating the Feasibility and Efficacy of Dose Timing (Morning vs Evening) of Temozolomide in the Treatment of Glioblastoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 4
- 主要终点
- Feasibility: adherence to TMZ dose timing protocol
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Unable or unwilling to complete study questionnaires
- •Metastatic or incurable cancer other than IDH-wild type glioblastoma
研究组 & 干预措施
Evening administration of TMZ
Participants were instructed to take the prescribed daily dose of temozolomide (TMZ) in the evening.
干预措施: Evening administration of TMZ (Other)
Morning administration of TMZ
Participants were instructed to take the prescribed daily dose of temozolomide (TMZ) in the morning.
干预措施: Morning administration of TMZ (Other)
结局指标
主要结局
Feasibility: adherence to TMZ dose timing protocol
时间窗: 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.
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.
次要结局
- Time to first progression(Disease assessment occurs prior to each TMZ cycle. Each TMZ cycle is 28 days. There is a maximum of 6 cycles.)
- Safety: rate of TMZ delay(TMZ delay is collected during the treatment period: post-cycle 1, post-cycle 2, post-cycle 3, post-cycle 4, post-cycle 5. Each TMZ cycle is 28 days. The rate of TMZ delay is calculated at Week 48.)
- 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.)
- Safety: reasons for early discontinuation of adjuvant TMZ(The reasons for early discontinuation of adjuvant TMZ will be collected during the treatment period: post-cycle 1, post-cycle 2, post-cycle 3, post-cycle 4, post-cycle 5. Each TMZ cycle is 28 days.)
- Treatment-related side effects(Modified FACT-Br GP1, GP2, and GP5 are collected within 1 month of each TMZ cycle (28-day cycle). Post-cycle 1, post-cycle 2, post-cycle 3, post-cycle 4, post-cycle 5, post-cycle 6.)
- 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.)
- Safety: reasons for early discontinuation of adjuvant TMZ(The reasons for early discontinuation of adjuvant TMZ will be collected during the treatment period: post-cycle 1, post-cycle 2, post-cycle 3, post-cycle 4, post-cycle 5. Each TMZ cycle is 28 days.)
- Safety: rate of TMZ delay(TMZ delay is collected during the treatment period: post-cycle 1, post-cycle 2, post-cycle 3, post-cycle 4, post-cycle 5. Each TMZ cycle is 28 days. The rate of TMZ delay is calculated at Week 48.)
- Health-related quality of life (HR-QoL): FACT-Br Version 4(Baseline and 4-, 8-, 12-, 24-, and 48-weeks after baseline.)
- HR-QoL: Time to HR-QoL deterioration(FACT-Br is collected at baseline and 4-, 8-, 12-, 24-, and 48-weeks after baseline..)
- Treatment-related side effects(Modified FACT-Br GP1, GP2, and GP5 are collected within 1 month of each TMZ cycle (28-day cycle). Post-cycle 1, post-cycle 2, post-cycle 3, post-cycle 4, post-cycle 5, post-cycle 6.)
- Change in Trial Outcome Index(Baseline to 12-weeks)
- Change in FACT-Br scores(FACT-Br is collected at baseline and 4-, 8-, 12-, 24-, and 48-weeks after baseline.)
- Time to first progression(Disease assessment occurs prior to each TMZ cycle. Each TMZ cycle is 28 days. There is a maximum of 6 cycles.)
- Overall survival(Overall survival is determined at 5-years after baseline.)
- Internal biological time of TMZ delivery(Post-Cycle 1. Each cycle is 28 days in length.)
- Wall clock time of TMZ administration(Post-Cycle 1. Each cycle is 28 days in length.)