Exercise to Prevent AnthrCycline-based Cardio-Toxicity Study (EXACT)

Exercise to Prevent AnthrCycline-based Cardio-Toxicity Study (EXACT)

As the numbers of cancer survivors grow, the long-term adverse effects of cancer therapy are becoming increasingly apparent. Most prominent are the toxic effects on the heart (cardiotoxicity) which may lead to cardiac dysfunction and increased risk of cardiovascular disease (CVD). The investigators hypothesize that an individualized aerobic training program for cancer patients receiving active treatment will be both feasible and safe and will result in improvements in overall levels of physical activity and quality of life.

Feasibility will be assessed by evaluating the recruitment, adherence and attrition rates, along with program safety. Efficacy will be assessed by evaluating changes in health-related outcomes.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Inflammation; Heart; Disease, Functional
• Intervention / Treatment: Other: Moderate Intensity Exercise

Detailed Description

As the numbers of cancer survivors grow, the long-term adverse effects of cancer therapy are becoming increasingly apparent. Most prominent are the toxic effects on the heart (cardiotoxicity) which may lead to cardiac dysfunction and increased risk of cardiovascular disease (CVD). Of note, data indicate that the magnitude of CVD risk for long-term survivors may exceed the risk of a secondary malignancy, which is a known complication of primary cancer therapy. While long-term follow-up data in adult cancer survivors is lacking, study of adult survivors of childhood cancers shows that these individuals are 15 times more likely to develop congestive heart failure (CHF), 10 times more likely to develop CVD, and 9 times more likely to suffer a stroke compared individuals who have not had cancer. Thus, it is clear that the long-term cardiotoxic effects of cancer therapy represent a significant concern for cancer survivors. The mechanisms responsible for the damaging effects of cancer therapy are not fully understood, however there is a need to maximize the benefits of treatment while minimizing long-term damage. Recent animal studies suggest that aerobic exercise training may offer a protective effect against chemotherapy-induced heart disease. However, to the investigator's knowledge, no study to date has examined the potential cardioprotective benefits of exercise training for patients receiving cancer treatment.

Accordingly, the purpose of this pilot study is to evaluate the feasibility and efficacy of a 12-week supervised exercise program based on the principles of cardiac rehabilitation for patients receiving anthracycline-based chemotherapy.

Feasibility will be assessed by evaluating three outcomes, recruitment rate, adherence rate (i.e. exercise class attendance records), attrition rate, and safety (i.e. number of adverse events).

Efficacy will be assessed by evaluating changes in health-related outcomes to assess if these changes are equal to or better than what was measured at baseline. The health-related outcomes include cardiac function and biological markers of cardiotoxicity.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • QEII Health Science Center, Nova Scotia Health Authority

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria - Only those patients who meet the following inclusion will be asked to participate in the study:

• Between the ages of 18 and 65;
• Receiving anthracycline chemotherapeutic treatment for a primary/non-recurrent breast or hematological malignancy;
• Are scheduled to received a minimum dose of 100 mg/m2 of doxorubicin (DOX) or 120 mg/m2 of daunorubicin (DAUN), or 150 mg/m2 epirubicin (EPI)
• Within eight weeks of first anthracycline dose;
• Do not have a previous history of myocardial infarction, cerebrovascular disease, peripheral vascular disease, congestive heart failure, or cardiomyopathy (controlled hypertension is not exclusionary);
• Have no known contraindications to light-to-moderate exercise;
• Have no known contraindications to cardiopulmonary exercise stress testing;
• Able to participate in the 12-week community-based exercise program;
• Provided medical consent from their treating physician

Exclusion Criteria:

• Any patients who meet the inclusion criteria, but have any significant cognitive limitations will be excluded from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Moderate Intensity Exercise; All consenting patients will participate in an aerobic training program, twice-weekly over a 12-week period. Assessments will be performed at baseline (pre-training) and post-program (12-weeks). All participants will continue to receive standard care for their cancer diagnosis.

Other: Moderate Intensity Exercise; Exercise sessions will be held twice-weekly and will begin with a group warm-up activity, followed by 45 minutes of aerobic activity and ending with a cool down. All aerobic exercise will be performed at a moderate intensity, defined as exercise that elicits a heart rate (HR) between 40-60% of heart rate reserve (HRR). Prior to the initial exercise session target heart rates will be calculated for each subject based on the maximum HR achieved during their baseline stress test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility as measured by rate of recruitment	The rate of recruitment will be measured by comparing the number of patients screened to the number of patients enrolled (patients per month).	12 Weeks
Number of adverse events	The number of adverse events associated with exercise program will be used to examine safety.	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility as measured by program adherence	The program adherence will be calculated by dividing the total number of exercise sessions by the number of actual session attended.	12 Weeks
Feasibility as measured by attrition rate	The attrition rate will be measured by the number of patients who drop out of the study.	12 Weeks
Cardiac Function	Cardiac function will be measured by examining heart chamber size, ventricular function and blood flow between the cardiac chambers using a Multigated acquisition (MUGA) scan.	12 Weeks
Cardiac Disease Risk	Cardiac disease risk will be measured using the Framingham Risk Score.	12 Weeks
Aerobic Fitness	Aerobic fitness will be measured by comparing baseline and 12 week cardiac stress tests and the associated peak oxygen uptake values.	12 Weeks
Fatigue	The Functional Assessment of Cancer Therapy - Fatigue questionnaire will be used to compare baseline and 12 week self-reported levels of fatigue.	12 Weeks
Physical Activity Behaviours	Baseline and 12 week levels of physical activity will be measured using the International Physical Activity Questionnaire.	12 Weeks
Life Quality	The Functional Assessment of Cancer Therapy - General questionnaire along with the appropriate tumor specific appendix, will be used to compare baseline and 12 week quality of life measures.	12 Weeks
Lipid Profile	Baseline and 12 week levels will be compared.	12 Weeks
Fasting Glucose	Baseline and 12 week levels will be compared.	12 Weeks
High-sensitivity Troponin (hs-TNT)	Baseline and 12 week levels will be compared.	12 Weeks
N-terminal of the prohormone brain natriuretic peptide (NTproBNP)	Baseline and 12 week levels will be compared.	12 Weeks
C-reactive protein (CRP)	Baseline and 12 week levels will be compared.	12 Weeks
Cytokines (IL-1α)	Baseline and 12 week levels (picogram per milileter) will be compared.	12 Weeks
Cytokines (IL-1β)	Baseline and 12 week levels (picogram per milileter) will be compared.	12 Weeks
Cytokines (IL-4)	Baseline and 12 week levels (picogram per milileter) will be compared.	12 Weeks
Cytokines (IL-6)	Baseline and 12 week levels (picogram per milileter) will be compared.	12 Weeks
Cytokines (IL-10)	Baseline and 12 week levels (picogram per milileter) will be compared.	12 Weeks
Cytokines (IL-17)	Baseline and 12 week levels (picogram per milileter) will be compared.	12 Weeks
Cytokines (TNFα)	Baseline and 12 week levels (picogram per milileter) will be compared.	12 Weeks

Collaborators and Investigators

• Sponsor: Nova Scotia Health Authority
• Investigators: Principal Investigator: Scott Grandy, PhD, Assistant Professor, Affiliate Scientist, Division of Cardiology, Nova Scotia Health Authority

Publications and helpful links

General Publications

• Albini A, Pennesi G, Donatelli F, Cammarota R, De Flora S, Noonan DM. Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention. J Natl Cancer Inst. 2010 Jan 6;102(1):14-25. doi: 10.1093/jnci/djp440. Epub 2009 Dec 10.
• Yeh ET. Cardiotoxicity induced by chemotherapy and antibody therapy. Annu Rev Med. 2006;57:485-98. doi: 10.1146/annurev.med.57.121304.131240.
• Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, Friedman DL, Marina N, Hobbie W, Kadan-Lottick NS, Schwartz CL, Leisenring W, Robison LL; Childhood Cancer Survivor Study. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006 Oct 12;355(15):1572-82. doi: 10.1056/NEJMsa060185.
• Keats MR, Grandy SA, Giacomantonio N, MacDonald D, Rajda M, Younis T. EXercise to prevent AnthrCycline-based Cardio-Toxicity (EXACT) in individuals with breast or hematological cancers: a feasibility study protocol. Pilot Feasibility Stud. 2016 Aug 5;2:44. doi: 10.1186/s40814-016-0084-9. eCollection 2016.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: May 11, 2015
• First Submitted That Met QC Criteria: June 11, 2015
• First Posted (Estimate): June 12, 2015

Study Record Updates

• Last Update Posted (Estimate): December 6, 2022
• Last Update Submitted That Met QC Criteria: December 2, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Exercise; Quality of Life; Complementary Therapies; Neoadjuvant Therapy; Feasibility Studies
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Wounds and Injuries; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Inflammation; Cardiotoxicity
• Other Study ID Numbers: EXACT2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No