The HIMALAYAS Trial and Lifestyle Changes in Pediatric, Adolescent and Young Adult Cancer Survivors Study: A Multicentre Randomized Controlled Trial

NCT05023785 | Recruiting DMC

• 1 other identifier: 23-5626
• Study Type: interventional
• Target: 336
• Locations: 1 country
• Sites: 1

Brief Summary

Pediatric, adolescent and young adult cancer survivors (PAYA-CS) are at higher risk of cardiovascular (CV) morbidity and mortality. This is a consequence of prior cancer-related therapies that have the potential of producing cardiac dysfunction, reducing cardiorespiratory fitness (reduced VO2peak) and psychosocial morbidities (i.e., anxiety and depression). A reduction of physical activity levels can evoke functional limitations resulting in a vicious cycle of reduced exercise tolerance and physical deterioration. To date, there is limited evidence on the use of non-pharmacological strategies such as Cardio-Oncology Rehabilitation (CORE) including structured exercise, behavioural support and risk factor management to improve the outcomes of this underserved population. The HIMALAYAS study is a randomized controlled trial designed to evaluate the impact of a CORE intervention (consisting of six-months home and onsite-based structured moderate to high-intensity aerobic exercise training and CVD risk factor management) on CV and psychosocial health, and the cardiovascular disease risk in PAYA-CS with mild heart dysfunction (stage B heart failure) compared to standard of care (i.e. providing guidance on the current exercise recommendations for cancer survivors). The primary objective of the HIMALAYAS study is to determine whether a six-month supervised CORE intervention, consisting of individualized moderate to high-intensity aerobic exercise training, CVD risk factor modification and enhanced online behavioral support, improves cardiorespiratory fitness (VO2peak; primary outcome), cardiac function, CVD risk factors and biomarkers, and patient-reported outcomes (PROs) at six- months follow-up compared to standard of care (CON) in PAYA-CS with stage B heart failure. The secondary objective is to assess the same outcomes at 12- and 24-months follow-up. We will recruit 336 patients across 5 sites in Canada and upto 134 patients at UHN in 3 years and conclude in 6 years.

Conditions

Heart Failure; Cardiotoxicity; Cancer

Keywords

Adolescents and Young Adults; Exercise Therapy; Behavioral and Peer Support; Cardiac Rehabilitation; Cancer Survivor

Outcome Measures

Primary Outcomes (1)

• Cardiorespiratory fitness

  Assessed via cardiopulmonary exercise test and quantified as VO2peak

  Baseline to 6-month follow-up (Primary RCT)

Secondary Outcomes (60)

• Cardiorespiratory fitness

  Baseline to 24-month follow-up (Primary and Secondary RCTs)

• Ventilatory threshold

  Baseline to 6-month follow-up (Primary RCT)

• Ventilatory threshold

  Baseline to 24-month follow-up (Primary and Secondary RCTs)

• Anaerobic threshold

  Baseline to 6-month follow-up (Primary RCT)

• Anaerobic threshold

  Baseline to 24-month follow-up (Primary and Secondary RCTs)

Other Outcomes (16)

• Therapeutic alliance

  Baseline to 6-month follow-up (Primary RCT)

• Testing Performance

  Study initiation to end of 66-month study period (Primary and Secondary RCTs)

• Serious and non-serious adverse events

  Study initiation to end of 66-month study period (Primary and Secondary RCTs)

Study Arms (2)

Cardio-Oncology Rehabilitation (CORE)

EXPERIMENTAL

Participants in the CORE group will have 1. A personalized, supervised exercise program ((in-person at intuition and virtual/ homebased exercises) 2. CV risk factor management, 3. behavioural support for the first 6 months. The behavioural support will continue for CORE participants from months 7-24. Behavioural support includes professionally guided and peer-enhanced exercise behavioural support based on behaviour change stage theories. CORE participants will be provided a wrist-worn heart and physical activity monitor to use throughout the 24-month observation period.

Behavioral: Cardio-oncology Rehabilitation (CORE)

Standard of Care (CON)

NO INTERVENTION

Participants in the CON group will receive standard medical care and physical activity will be monitored by a wrist-worn activity tracker for 2 years.

Interventions

Cardio-oncology Rehabilitation (CORE) BEHAVIORAL

Exercise therapy, CVD risk factor management for the first 6 months (as per current standards in CR models) and behavioural support for the entire 2-year intervention period

Cardio-Oncology Rehabilitation (CORE)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Be a PAYA-CS, defined as ≤39 years of age at the time of cancer diagnosis;
• Be 18-45 years of age at the time of enrolment;
• Received cancer treatment(s) with known cardiovascular risks (e.g., anthracyclines, trastuzumab, radiotherapy, platinum-based agents, vascular endothelial growth factor inhibitors, tyrosine kinase inhibitors);
• Be cancer-free at the time of enrollment;
• Stage B Heart Failure (SBHF)
• In patients with availability of pre-treatment imaging:
• ≥10% decrease in LVEF at post-treatment compared to pre-treatment
• ≥15% decrease in GLS at post-treatment compared to pre-treatment
• No pre-treatment imaging:
• LVEF ≤53% in women/51% in men
• GLS \>-18%
• Left ventricular hypertrophy (LV mass/body surface area: \>95 g/m2 for women or \>115 g/m2 for men)
• Concentric remodelling (\>0.42 relative wall thickness)
• Diastolic dysfunction (≥ grade 1)
• BNP ≥35pg/ml or NT-proBNP ≥125pg/ml

You may not qualify if:

• Have an absolute or unresolved relative contraindication to exercise according to the American College of Sports Medicine guidelines;
• Have an untreated physical or mental health concern that precludes safe and effective exercise participation;
• Have established CVD (excluding mildly reduced LVEF as described above);
• Be pregnant at time of recruitment;
• Be currently engaging in frequent high-intensity exercise (\>1 high-intensity exercise session per week);
• Have substantial barriers to participating, including (1) living too far from study centre or (2) being unable or willing to comply with the study protocol.

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): collaborator
• University Health Network, Toronto: lead
• Queen Elizabeth II Health Sciences Centre: collaborator
• Alberta Health services: collaborator
• Vancouver General Hospital: collaborator
• Université de Montréal: collaborator
• Dalhousie University: collaborator
• University of Alberta: collaborator
• University of British Columbia: collaborator
• University of Toronto: collaborator

Study Sites (1)

University Health Network

Toronto, Ontario, M5G2C4, Canada

RECRUITING

MeSH Terms

Conditions

Heart Failure; Cardiotoxicity; Neoplasms; Behavior

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Central Study Contacts

Paaladinesh Thavendiranathan, MD

CONTACT

416-340-5326; dinesh.thavendiranathan@uhn.ca

Nilina Mohabir, MSc

CONTACT

437-677-7491; nilina.mohabir@uhn.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: August 27, 2021
• Study Start: January 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

CA (1)