Clinical trial NCT02471053: Exercise to Prevent AnthrCycline-based Cardio-Toxicity Study
Official title: Exercise to Prevent AnthrCycline-based Cardio-Toxicity Study (EXACT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Neoplasms
Heart; Disease, Functional
Inflammation
Keywords: Exercise
Quality of Life
Complementary Therapies
Neoadjuvant Therapy
Feasibility Studies
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
First posted: 2015-06-12
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Feasibility as measured by rate of recruitment
timeFrame: 12 Weeks
measure: Number of adverse events
timeFrame: 12 Weeks
Secondary outcomes:
measure: Feasibility as measured by program adherence
timeFrame: 12 Weeks
measure: Feasibility as measured by attrition rate
timeFrame: 12 Weeks
measure: Cardiac Function
timeFrame: 12 Weeks
measure: Cardiac Disease Risk
timeFrame: 12 Weeks
measure: Aerobic Fitness
timeFrame: 12 Weeks
measure: Fatigue
timeFrame: 12 Weeks
measure: Physical Activity Behaviours
timeFrame: 12 Weeks
measure: Life Quality
timeFrame: 12 Weeks
measure: Lipid Profile
timeFrame: 12 Weeks
measure: Fasting Glucose
timeFrame: 12 Weeks
measure: High-sensitivity Troponin (hs-TNT)
timeFrame: 12 Weeks
measure: N-terminal of the prohormone brain natriuretic peptide (NTproBNP)
timeFrame: 12 Weeks
measure: C-reactive protein (CRP)
timeFrame: 12 Weeks
measure: Cytokines (IL-1α)
timeFrame: 12 Weeks
measure: Cytokines (IL-1β)
timeFrame: 12 Weeks
measure: Cytokines (IL-4)
timeFrame: 12 Weeks
measure: Cytokines (IL-6)
timeFrame: 12 Weeks
measure: Cytokines (IL-10)
timeFrame: 12 Weeks
measure: Cytokines (IL-17)
timeFrame: 12 Weeks
measure: Cytokines (TNFα)
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Halifax
country: Canada
facility: QEII Health Science Center, Nova Scotia Health Authority
state: Nova Scotia
Study officials:
affiliation: Assistant Professor, Affiliate Scientist, Division of Cardiology, Nova Scotia Health Authority
name: Scott Grandy, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Yeh ET. Cardiotoxicity induced by chemotherapy and antibody therapy. Annu Rev Med. 2006;57:485-98. doi: 10.1146/annurev.med.57.121304.131240.
citation: 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.
citation: 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.