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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cancer (Solid Tumors); Geriatric Oncology
• Intervention / Treatment: Other: TRTRM-guided risk-stratified treatment strategy

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.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wing-Lok Wendy Chan, MBBS; Phone Number: 5124 852-22553111; Email: winglok@hku.hk
• Study Contact Backup: Name: Horace Shek, BSc; Phone Number: 4352 852-22553111; Email: oncology@hku.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong SAR
    • Contact: Wing Lok Chan; Phone Number: (852) 2255-3111; Email: winglok@hku.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 65 or above
2. A diagnosis of lung cancer, gastrointestinal cancer, breast cancer, prostate cancer, and uterine cancer with histological confirmation or radiological diagnosis**
3. 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.
4. ECOG performance status of 0-2
5. Agreement for treatment according to the TRTRM (ACTTOP) -risk strategy if in the TRTRM (ACTTOP) -informed care group
6. Fluent in English or Chinese
7. 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:

1. Planned for radiotherapy alone
2. Planned for systemic treatment concomitant with radiotherapy
3. Scheduled to have hormonal therapy alone e.g. tamoxifen, aromatase inhibitors, luteinizing hormone-releasing hormone agonist (LHRHa)
4. Planned for surgery within 3 months
5. Dementia or patient mentally not fit for consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: 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).
Experimental: 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.	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. Intermediate- or high-risk patients starting chemotherapy begin treatment at 60% dose intensity using a "start-low, go-slow" strategy, with dose escalation based on tolerance. Patients receiving targeted therapy or immunotherapy follow standard local dosing protocols without TRTRM/ACTTOP-guided dose modification. Intermediate- and high-risk patients receive weekly monitoring by healthcare professionals during the initial treatment period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Grade 3 or Higher Treatment-Related Toxicities	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.	2 months after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Emergency Department Visits Due to Treatment-Related Toxicities	Number of participants who experience one or more unplanned emergency department visits attributed to treatment-related toxicities, determined through review of clinical records.	2 months after treatment initiation
Number of Participants with Unplanned Hospitalizations Due to Treatment-Related Toxicities	Number of participants who experience one or more unplanned hospitalizations attributable to treatment-related toxicities, identified through review of electronic medical records.	2 months after treatment initiation
Number of Participants with Premature Termination of Systemic Anti-Cancer Treatment Due to Treatment-Related Toxicities	Premature termination of systemic anti-cancer treatment due to treatment-related toxicities, defined as inability to complete all planned cycles in the adjuvant setting or the first four cycles in the palliative setting. Treatment discontinuation will be verified via clinical records.	Within 2 months of treatment initiation
Early Mortality	Death occurring within three months of starting systemic anti-cancer treatment.	Within 3 months of treatment initiation
Change in Quality of Life	Change in health-related quality of life measured using the Global Health Status scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). The Global Health Status scale consists of two items assessing overall health and overall quality of life, each rated on a 7-point scale from 1 (very poor) to 7 (excellent). Raw scores are transformed to a 0-100 scale according to EORTC scoring guidelines, with higher scores indicating better overall health-related quality of life.	Baseline to 2 months after treatment initiation
Overall Survival	Time from treatment initiation to death from any cause.	Baseline to 2 years

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Wing-Lok Wendy Chan, MBBS, The University of Hong Kong

Publications and helpful links

Helpful Links

• Additional study information is available at the HKU Clinical Trials Registry

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): July 31, 2030

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: geriatrics; Older patients; toxicities; prediction model; ACTTOP
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CIRB-2025-629-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared because data sharing was not approved by the Institutional Review Board and was not included in the informed consent.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No