Cancer Adverse Effects PReventIon With Care & Exercise: the CAPRICE Study

NCT03850171 | Terminated DMC

• 1 other identifier: CAPRICE
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 4

Brief Summary

Breast cancer is the most common cancer among women worldwide. Similarly, Hodgkin and non- Hodgkin lymphomas make up two of the most prevalent cancers in men and women. Even though remarkable improvements in cancer-free survival have been achieved in the last decades, the development of cardiac toxicity, associated with anthracycline-based chemotherapy (Anth-bC) counteracts the improvements in survival in these patient groups. One of the first clinical manifestation of Anth-bC cardiotoxicity is diastolic dysfunction, with further symptoms being left ventricular dysfunction and heart failure as well as a decline in exercise tolerance. Besides the direct cardiotoxic effects of anticancer treatment, many drugs also have adverse effects on the vascular endothelium. The concept of 'Exercise is Medicine' has become well established in exercise-oncology research. Exercise therapy is now considered a safe and well-tolerated adjunct therapy inducing beneficial effects on body composition, aerobic fitness and muscular strength, pain and fatigue, quality of life (QoL), depressive symptoms, and all cause survival. However, there is insufficient data on the superiority of performing exercise training therapy before and during chemotherapy with regard to cardiotoxic and cardiovascular side effects. Further, there is no data on patient preference for and barriers toward different timings of exercise training therapy. Therefore, the aim of the study is to compare left ventricular (LV) function measured by LV global longitudinal strain (GLS) in breast cancer and lymphoma patients undergoing Anth-bC randomised to completing an exercise-based rehabilitation programme during chemotherapy to those randomised to complete the programme after chemotherapy. Further, blood samples will be drawn to analyse biomarkers of myocardial injury (brain natriuretic peptide and high-sensitive cardiac troponin). Additional measurements include aortic distensibility as part of the echocardiographic examination and exercise capacity through cardiopulmonary exercise testing. QoL and fatigue will be assessed in a questionnaire, compliance with exercise training through monitoring and patient preference at 3 and 6 months will be evaluated through an interview. Cardiovascular risk factors will be assessed through body composition, 24h ambulatory blood pressure monitoring, 24h electrocardiogram and the analysis of established blood markers. Women and men aged 18 years and older with histologically confirmed breast cancer or lymphoma (ECOG grade 0-2) who are Anth-bC naïve and with reasonable life expectancy will be included in the study. The exercise programme is part of onco-rehabilitation programmes at the Inselspital Bern, the Spital AG Thun and the Bürgerspital Solothurn. Programmes last for 12 weeks and offer two supervised sessions per week (@ 60-90 min). They usually contain an endurance component (e.g. 40 min of cycling) and a strength, agility or relaxation component. Patients are encouraged to complete a third exercise session per week at home or elsewhere. Home-based training and general physical activity will be assessed by a questionnaire and an activity monitor. A total of 120 patients will be recruited. Measurements will be performed at baseline, after 3 months (week 13) and after 6 months (week 26).

Conditions

Breast Neoplasm Female; Lymphoma; Cardiotoxicity; Anthracyclines; Physical Activity

Keywords

Breast Cancer; Exercise Training Therapy; Global longitudinal strain; Barriers; Left ventricular dysfunction; Heart failure; Breast disease; Exercise rehabilitation; Lymphoma

Outcome Measures

Primary Outcomes (1)

• Changes from baseline in left ventricular (LV) global longitudinal strain (GLS)

  GLS assessed by speckle tracking echocardiography is an established marker for LV systolic function with a good reproducibility, which has also been found in the investigators' laboratory. In breast cancer and lymphoma patients LV global longitudinal strain is an established measure to assess cardiotoxicity of Anth-bC.

  week 13

Secondary Outcomes (8)

• Change in Blood biomarkers

  week 0, 13, and 26

• Identification of barriers towards exercise training

  week 13 and 26

• Compliance with exercise training

  week 0, 13 and 26

• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)

  week 0, 13, and 26

• Vascular function

  week 0, 13, and 26

Study Arms (2)

ExEarly

EXPERIMENTAL

Patients completing the exercise training concurrent to anthracycline chemotherapy treatment during months 1 to 3

Other: Exercise Training

ExStandard

NO INTERVENTION

Patients will be encouraged to continue with their regular physical activity routine and will be medically managed as per standard of care by their Cardiologist and Oncologists.

Interventions

Exercise Training OTHER

Participants from the experimental study arm are assigned to a 12-week exercise training programme integrated in a multidisciplinary oncology rehabilitation programme at the Inselspital Bern, Spital AG Thun, or Bürgerspital Solothurn. The exercise programme will comprise 2 weekly exercise sessions lasting 90 min, supervised by experienced exercise therapists. The sessions start with approximately 40 min cycling on an ergometer at moderate intensity, increasing on a weekly basis if possible. After the cycling training, patients continue the exercise session with 40 min of strength training, stretching, relaxation, coordination and balance training. In addition, patients will be instructed to perform at least one additional endurance-related activity per week in their own time with a duration of 30-60 min at moderate intensity levels (e.g. walking, bicycling).

ExEarly

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women and men aged 18 years and older
• Histologically confirmed breast cancer or lymphoma
• Anth-bC naïve
• Scheduled for first-line Anth-bC
• Eastern Cooperative Oncology Group (ECOG) grade 0-2
• Curative or palliative approach with reasonable life expectancy
• Willingness to attend exercise sessions twice per week for 12 weeks (24 sessions in total)
• Informed Consent as documented by signature (Appendix Informed Consent Form)

You may not qualify if:

• Inability to participate in a 3-month training program
• Contraindication to maximal CPET
• Cancer-specific contraindications including safety blood parameters
• Previous radiotherapy of the mediastinum and/or the the left breast
• Structural heart disease with reduced left ventricular ejection fraction (EF\<50%)
• Valvular heart disease with more than mild regurgitation or stenosis
• Heart rhythms other than sinus rhythm
• Pacemaker with permanent ventricular stimulation
• Antihypertensive medication (e.g. ACE inhibitors/ATII blockers, Ca channel blocker, beta blockers)
• Known or suspected non-compliance, drug or alcohol abuse
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
• Previous enrolment into the current study
• Enrolment of the investigator, his/her family members, employees and other dependent persons

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Spital STS AG: collaborator
• Bürgerspital Solothurn: collaborator
• Lindenhofspital: collaborator
• University of Bern: collaborator

Study Sites (4)

Lindenhofgruppe

Bern, 3001, Switzerland

Location

University Clinic for Cardiology

Bern, 3010, Switzerland

Location

Bürgerspital Solothurn

Solothurn, 4500, Switzerland

Location

Spital STS AG

Thun, 3600, Switzerland

Location

Related Publications (1)

• Schneider C, Ryffel C, Stutz L, Rabaglio M, Suter TM, Campbell KL, Eser P, Wilhelm M. Supervised exercise training in patients with cancer during anthracycline-based chemotherapy to mitigate cardiotoxicity: a randomized-controlled-trial. Front Cardiovasc Med. 2023 Dec 4;10:1283153. doi: 10.3389/fcvm.2023.1283153. eCollection 2023.

  PMID: 38111886 DERIVED

MeSH Terms

Conditions

Lymphoma; Cardiotoxicity; Motor Activity; Breast Neoplasms; Ventricular Dysfunction, Left; Heart Failure; Breast Diseases

Interventions

Exercise

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; 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; Behavior; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Ventricular Dysfunction

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Matthias Wilhelm, Prof. Dr.

  University Clinic for Cardiology, University Hospital Berne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Assessors of outcome data and analysis will be blinded to the intervention arm.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised, controlled; parallel arm design.

Study Record Dates

• First Submitted: February 18, 2019
• First Posted: February 21, 2019
• Study Start: May 1, 2019
• Primary Completion: December 31, 2022
• Study Completion: January 31, 2023
• Last Updated: February 27, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

CH (4)