TRTRM (ACTTOP) -Guided Dosing Strategy in Older Patients With Cancer

Official title

Clinical Utility of the Treatment-related Toxicity Risk Model (TRTRM/ ACTTOP) in Older Patients With Cancer: a Randomised Controlled Trial

Overview

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.

Detailed description

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.

Interventions

• Other TRTRM-guided risk-stratified treatment strategy
  The Treatment-Related Toxicity Risk Model (TRTRM/ACTTOP) is used prospectively as a clinical decision-support tool to guide treatment dosing and monitoring in older patients starting systemic anti-cancer therapy. The TRTRM/ACTTOP stratifies patients into low-, intermediate-, or high-risk categories for severe treatment-related toxicities. Dose modification based on TRTRM risk category applies only to patients receiving chemotherapy. Low-risk patients receive 80% to full-dose chemotherapy. Inter

Primary outcome measures

• Incidence of Grade 3 or Higher Treatment-Related Toxicities [Time frame: 2 months after treatment initiation]

Secondary outcome measures (6)

• Number of Participants with Emergency Department Visits Due to Treatment-Related Toxicities [Time frame: 2 months after treatment initiation]
• Number of Participants with Unplanned Hospitalizations Due to Treatment-Related Toxicities [Time frame: 2 months after treatment initiation]
• Number of Participants with Premature Termination of Systemic Anti-Cancer Treatment Due to Treatment-Related Toxicities [Time frame: Within 2 months of treatment initiation]
• Early Mortality [Time frame: Within 3 months of treatment initiation]
• Change in Quality of Life [Time frame: Baseline to 2 months after treatment initiation]
• Overall Survival [Time frame: Baseline to 2 years]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Supportive care

Study locations

Hong Kong · 1 center

• Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, the — Hong Kong

Identifiers

NCT: NCT07484932 · CIRB-2025-629-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗