Clinical Utility of the Treatment-related Toxicity Risk Model (TRTRM/ ACTTOP) in Older Patients With Cancer: a Randomised Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- Incidence of Grade 3 or Higher Treatment-Related Toxicities
研究概览
简要总结
Older adults receiving systemic cancer treatments are at increased risk of developing severe treatment-related toxicities (TRT). Existing prediction tools such as CARG and CRASH have limited applicability in Chinese populations and do not fully address toxicities associated with newer therapies, including immunotherapy and targeted agents. The Treatment-related Toxicity Risk Model (TRTRM) was recently developed and validated in Hong Kong using data from 700 older cancer patients and has demonstrated better predictive accuracy and clinical relevance compared with existing tools.
This multi-center, open-label, randomized controlled trial aims to evaluate the clinical utility of the TRTRM by guiding treatment dose intensity and monitoring strategies. Participants aged 65 years or older who are starting a new systemic anti-cancer treatment will be randomized in a 1:1 ratio to receive either usual care or TRTRM-informed care. In the intervention arm, patients identified as having intermediate or high risk of toxicity will receive a "start-low, go-slow" dosing strategy with close monitoring, while low-risk patients will receive standard dosing.
The primary outcome is the incidence of grade 3 or higher treatment-related toxicities within the first two months of treatment initiation. Secondary outcomes include emergency visits, unplanned hospitalizations, premature treatment termination, early mortality, quality of life, and overall survival.
详细描述
This is a multi-center, open-label, prospective, randomized controlled trial designed to assess the clinical utility of the Treatment-Related Toxicity Risk Model (TRTRM/ ACTTOP) in reducing severe treatment-related toxicities in older patients with cancer undergoing systemic anti-cancer therapy.
Participants aged 65 years or older who are scheduled to start a new systemic anti-cancer treatment, including chemotherapy, targeted therapy, or immunotherapy, will be recruited from outpatient oncology clinics at four public hospitals in Hong Kong. Eligible participants will be randomized in a 1:1 ratio to either a usual care group or a TRTRM (ACTTOP) -informed care group using a computer-generated block randomization scheme, stratified by treatment type (chemotherapy-containing versus non-chemotherapy-containing regimens) and treatment intent (radical versus palliative).
In the usual care group, treating oncologists will manage patients according to standard clinical practice without access to the TRTRM (ACTTOP) score. In the TRTRM-informed care group, the TRTRM (ACTTOP) score will be calculated prior to treatment initiation and used to guide treatment decisions. Patients classified as low risk will receive 80% to full standard dose. Patients classified as intermediate or high risk who are receiving chemotherapy will start treatment at 60% dose intensity, with dose escalation based on treatment tolerance. Patients receiving targeted therapy or immunotherapy will receive standard dosing according to local protocols. Intermediate- and high-risk patients will also receive weekly monitoring by healthcare professionals via telephone or remote systems during the initial treatment period.
The primary endpoint is the incidence of grade 3 or higher treatment-related toxicities as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 within the first two months of treatment initiation. Secondary endpoints include emergency visits and unplanned hospitalizations due to treatment-related toxicities, premature treatment termination, early mortality within three months, changes in quality of life measured by the EORTC QLQ-C30 Global Health Status scale, and overall survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Outcomes Assessor)
盲法说明
The study is open-label to participants and treating clinicians due to the nature of the intervention, which involves dose modification and clinical monitoring based on the Treatment-Related Toxicity Risk Model (TRTRM/ ACTTOP).
Outcome assessors responsible for determining study endpoints, including treatment-related toxicities, emergency visits, hospitalizations, and mortality, are blinded to treatment allocation. Outcome data are obtained through independent review of electronic medical records and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 without access to group assignment.
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 65 or above
- •A diagnosis of lung cancer, gastrointestinal cancer, breast cancer, prostate cancer, and uterine cancer with histological confirmation or radiological diagnosis**
- •Seen by the oncologist and scheduled to receive a new systemic anti-cancer treatment, including chemotherapy, targeted therapy, and immunotherapy, in either radical or first/second-line palliative intent. The planned treatment regimen is expected to last for at least 3 months.
- •ECOG performance status of 0-2
- •Agreement for treatment according to the TRTRM (ACTTOP) -risk strategy if in the TRTRM (ACTTOP) -informed care group
- •Fluent in English or Chinese
- •Valid consent obtained ** Only these five types of cancer are included to reduce the heterogeneity of the patients, as they are the top 5 cancers in Hong Kong.
排除标准
- •Planned for radiotherapy alone
- •Planned for systemic treatment concomitant with radiotherapy
- •Scheduled to have hormonal therapy alone e.g. tamoxifen, aromatase inhibitors, luteinizing hormone-releasing hormone agonist (LHRHa)
- •Planned for surgery within 3 months
- •Dementia or patient mentally not fit for consent
研究组 & 干预措施
Usual care
Participants in the usual care arm receive standard physician-determined systemic anti-cancer treatment. Treatment dose intensity and monitoring are determined by the treating clinician according to routine clinical practice without access to the Treatment-Related Toxicity Risk Model (TRTRM/ ACTTOP).
Intervention group (TRTRM-informed care)
Participants in the TRTRM (ACTTOP) -informed care arm receive systemic anti-cancer treatment guided by the Treatment-Related Toxicity Risk Model (TRTRM/ ACTTOP). The TRTRM (ACTTOP) is used to stratify patients into low-, intermediate-, or high-risk categories for severe treatment-related toxicities and to guide treatment dose intensity and monitoring strategies.
Treatment dose intensity is guided by TRTRM (ACTTOP) risk category. Patients classified as low risk receive 80% to full-dose chemotherapy. Patients classified as intermediate or high risk who are starting chemotherapy begin treatment at 60% dose intensity using a "start-low, go-slow" escalation strategy based on treatment tolerance. Patients receiving targeted therapy or immunotherapy follow local dosing protocols.
Intermediate- and high-risk patients receive weekly monitoring by healthcare professionals via telephone or a remote monitoring system.
干预措施: TRTRM-guided risk-stratified treatment strategy (Other)
结局指标
主要结局
Incidence of Grade 3 or Higher Treatment-Related Toxicities
时间窗: 2 months after treatment initiation
Incidence of grade 3 or higher treatment-related toxicities as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
次要结局
- Number of Participants with Emergency Department Visits Due to Treatment-Related Toxicities(2 months after treatment initiation)
- Number of Participants with Unplanned Hospitalizations Due to Treatment-Related Toxicities(2 months after treatment initiation)
- Number of Participants with Premature Termination of Systemic Anti-Cancer Treatment Due to Treatment-Related Toxicities(Within 2 months of treatment initiation)
- Early Mortality(Within 3 months of treatment initiation)
- Change in Quality of Life(Baseline to 2 months after treatment initiation)
- Overall Survival(Baseline to 2 years)
研究者
Wing Lok Wendy Chan
Clinical Associate Professor
The University of Hong Kong