Understanding and Predicting Breast Cancer Events After Treatment (UPBEAT)

• ClinicalTrials.gov Identifier: NCT02791581
• Recruitment Status: Active, not recruiting
• First Posted: June 7, 2016
• Last Update Posted: January 24, 2024
• Sponsor: Wake Forest University Health Sciences
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Wake Forest University Health Sciences

Tracking Information

• First Submitted Date: May 20, 2016
• First Posted Date: June 7, 2016
• Last Update Posted Date: January 24, 2024
• Actual Study Start Date: July 21, 2017
• Estimated Primary Completion Date: November 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 31, 2016)

• FACT-Fatigue [ Time Frame: Baseline ]
  Participants rate the degree to which each item applies in the past 7 days prior to Baseline using a 5-point scale. Scores range from 0-52, with higher scores indicating greater fatigue.
• Change in FACT-Fatigue Results [ Time Frame: Baseline and 3 months ]
  Participants rate the degree to which each item applies in the past 7 days using a 5-point scale. Scores range from 0-52, with higher scores indicating greater fatigue.
• Change in FACT-Fatigue Results [ Time Frame: Baseline, 3 months and 12 months ]
  Participants rate the degree to which each item applies in the past 7 days using a 5-point scale. Scores range from 0-52, with higher scores indicating greater fatigue.
• Change in FACT-Fatigue Results [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Participants rate the degree to which each item applies in the past 7 days using a 5-point scale. Scores range from 0-52, with higher scores indicating greater fatigue.
• Change in MRI Exam Results [ Time Frame: Baseline, 3 months and 24 months ]
  The exam will measure left ventricular volumes, ejection fraction, myocardial strain/strain rate, mass, mapping, aortic pulse wave velocity and aortic wall thickness. The exam will take 10 - 15 minutes to complete.
• Change in 6 Minute Walk Results [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  The purpose of this test is to find out how far the participant can walk in 6 minutes.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 2, 2019)

• Cohen's 4-item Perceived Stress Scale (PSS) [ Time Frame: Baseline, 3 months, 12 months, and 24 months ]
  A summed scale asking how often over the prior two weeks four aspects of stress were experienced (1=never to 5=very often) o weeks four aspects of stress were experienced (1=never to 5=very often)
• Cook-Medley Hostility Scale [ Time Frame: Baseline ]
  A 14-item scale used to assess the effect of hostility associated with cardiovascular risk factors. Minimum Score: 0 Maximum Score: 13 Higher values indicate greater hostility.
• Changes in FACT-Fatigue Results [ Time Frame: Baseline, 3 months, 12 months, and 24 months ]
  Participants rate the degree to which each item applies in the past 7 days using a 5-point scale. Scores range from 0-52, with higher scores indicating greater fatigue.
• 6 Minute Walk Results [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  The purpose of this test is to find out how far the participant can walk in 6 minutes.
• RAND MOS 36-item Short Form Health Survey (SF-36) [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  SF-36 consists of 36 items measuring the following 8 domains: physical function, role limitations due to physical health problems, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional health problems, and mental health. These 8 domains also provide two summary scores.
• Center for Epidemiological Studies Depression Scale (CESD-10) [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Screening questionnaire assessing depressive symptoms during the last week
• Godin Leisure-Time Exercise Questionnaire (LTEQ) [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Main process measure of physical activity participation
• PACE Adult Sedentary Behaviors Survey [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Assess sedentary lifestyle behaviors
• PROMIS Short Form 8A Measure of Sleep Disturbance [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Assess time course and risk factors associated with sleep disturbance and fatigue Minimum Score: Raw: 8, T-score: 28.9 Maximum Score: Raw: 40, T-score: 76.5 Higher values represent greater sleep disturbance.
• PROMIS Applied Cognitive Abilities Short Form 8A and Applied Cognition General Concerns Short Form 8A [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Measurement of different aspects of cognitive functioning. PROMIS Applied Cognitive Abilities Short Form 8A - Minimum Score: Raw: 8, T-score: 27.0 Maximum Score: Raw: 40, T-score: 64.8 Higher values represent better cognition. Applied Cognition General Concerns Short Form 8A - Minimum Score: Raw: 8, T-score: 23.3 Maximum Score: Raw: 40, T-score: 62.7 Higher values represent better cognition.
• Walking Efficacy for Duration Scale [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Comprised of six items and will be included as a measure of exercise capacity
• Chair Stands - Measures Leg Strength [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Participants will be first asked to stand from a sitting position without using their arms. If they can perform the task, they will then be asked to stand up and sit down five times as quickly as possible. The time to complete the task will be recorded.
• Standing Balance Test [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Participants will be asked to maintain balance for up to 30 seconds in three positions characterized by a progressive narrowing of the base support.
• Gait Speed Test [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Participants will be instructed to start at a marked walking course with toes touching the start line and when cued to start, will begin walking at their ususal speed. The time to walk from the starting line to the end of the 4-meter walk will be recorded.
• Grip Strength [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Grip strength is assessed with an isometric handgrip dynamometer while the participant is sitting with the head facing straight ahead. The elbow should be bent at a 90 degree angle and the wrist should be at the mid-prone position.
• Range of Motion [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Range of motion at the shoulder joint will be assessed with shoulder flexion and shoulder abduction with a goniometer.
• KCCQ-12 Questionnaire [ Time Frame: Baseline, 24 months ]
  Independently measures the patient's perception of their health status which includes heart failure symptoms (frequency and burden), physical and social limitations, and how their heart failure impacts their QOL within a 2-week recall period.

Original Secondary Outcome Measures (submitted: May 31, 2016)

• Cohen's 4-item Perceived Stress Scale (PSS) [ Time Frame: Baseline, 3 months, 12 months, and 24 months ]
  A summed scale asking how often over the prior two weeks four aspects of stress were experienced (1=never to 5=very often) o weeks four aspects of stress were experienced (1=never to 5=very often)
• Changes in FACT-Fatigue Results [ Time Frame: Baseline, 3 months, 12 months, and 24 months ]
  Participants rate the degree to which each item applies in the past 7 days using a 5-point scale. Scores range from 0-52, with higher scores indicating greater fatigue.
• 6 Minute Walk Results [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  The purpose of this test is to find out how far the participant can walk in 6 minutes.
• MOS 36-item Short Form Health Survey (SF-36) [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  SF-36 consists of 36 items measuring the following 8 domains: physical function, role limitations due to physical health problems, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional health problems, and mental health. These 8 domains also provide two summary scores.
• Center for Epidemiological Studies Depression Scale (CESD-10) [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Screening questionnaire assessing depressive symptoms during the last week
• Godin Leisure-Time Exercise Questionnaire (LTEQ) [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Main process measure of physical activity participation
• PACE Adult Sedentary Behaviors Survey [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Assess sedentary lifestyle behaviors
• Chair Stands - Measures Leg Strength [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Participants will be first asked to stand from a sitting position without using their arms. If they can perform the task, they will then be asked to stand up and sit down five times as quickly as possible. The time to complete the task will be recorded.
• Standing Balance Test [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Participants will be asked to maintain balance for up to 30 seconds in three positions characterized by a progressive narrowing of the base support.
• Grip Strength [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Grip strength is assessed with an isometric handgrip dynamometer while the participant is sitting behind a table with upper arm next to the body and elbow resting on the table with the head facing straight ahead.
• Range of Motion [ Time Frame: Baseline, 3 months, 12 months and 24 months ]
  Range of motion at the shoulder joint will be assessed with shoulder flexion and shoulder abduction with a goniometer.

Current Other Pre-specified Outcome Measures (submitted: May 31, 2016)

• B-type natriuretic peptide (BNP) [ Time Frame: Baseline and 24 months ]
  Serum BNP as a predictor of exercise intolerance
• Troponin - 1 [ Time Frame: Baseline and 3 months ]
  Acquired to determine associations between troponin levels during therapy and the onset of cardiac and vascular dysfunction, exercise capacity, and fatigue.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Understanding and Predicting Breast Cancer Events After Treatment
• Official Title: Understanding and Predicting Breast Cancer Events After Treatment (UPBEAT)
• Brief Summary: This study is being done to see if patients receiving chemotherapy for breast cancer affects the heart, the ability to exercise and fatigue when compared to patients who do not have cancer.

Detailed Description

840 women aged ≥18 years old scheduled to receive chemotherapy for Stage I-III breast cancer and a comparison population of 160 women without cancer (1,000 total). Equal numbers of women will be recruited aged < 52 vs. > 52. At baseline, innovative MRI measures of CV function (LV and aorta); measurements of submaximal (6-minute walk) and, on 45% of the cohort, maximal (peak VO2) exercise capacity; questionnaire data to assess fatigue and behavioral and psychosocial risk factors; and biomarkers will be collected.

Measurements will be repeated at 3±1, 12±2 and 24±2 months. This study will assess the relevance of pre-existing factors such as age, black/white race, hypertension, smoking (yes/no), diabetes, coronary artery disease, menopause status, CV medications, and physical activity on the study outcomes. Also, this study will assess dynamic change in modifiable CV risk factors (including BMI, blood pressure, serum lipids, serum glucose, physical activity, psychosocial factors, lifestyle behaviors), and the cancer treatment including chemotherapy, radiation therapy, immunotherapy, and surgery.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Breast Cancer

Intervention

Diagnostic Test: Cardiac MRI

Breast Cancer Patients Cardiac MRIs will be performed baseline, 3 months (for cancer patients only), and 24 months.

Non-Cancer Controls Cardiac MRIs will be performed baseline and 24 months.

Study Arms

• Experimental: Breast Cancer Patients

  Breast cancer patients receiving non-anthracycline or anthracycline chemotherapy Cardiac MRIs will be performed baseline, 3 months (for cancer patients only), and 24 months.

  Baseline: Collect innovative MRI measures of CV function (LV and aorta); measurements of submaximal (6-minute walk) and, on 45% of the cohort, maximal (peak VO2) exercise capacity; questionnaire data to assess fatigue and behavioral and psychosocial risk factors; and biomarkers.

  Measurements will be repeated at 3±1, 12±2 and 24±2 months after initiation of chemotherapy treatment.

  Intervention: Diagnostic Test: Cardiac MRI
• Experimental: Non-Cancer Controls

  Non-Cancer Controls Cardiac MRIs will be performed baseline and 24 months. Baseline: Collect innovative MRI measures of CV function (LV and aorta); measurements of submaximal (6-minute walk) and, 45% of the cohort, maximal (peak VO2) exercise capacity; questionnaire data to assess fatigue and behavioral and psychosocial risk factors; and biomarkers.

  Measurements will be repeated at 3±1, 12±2 (after the completion of radiation) and 24±2 months after initiation of baseline activities.

  Intervention: Diagnostic Test: Cardiac MRI

• Publications *: Bellissimo MP, Canada JM, Jordan JH, Ladd AC, Heiston EM, Brubaker P, Mihalko SL, Reding K, D Agostino R, O Connell N, Hackney MH, Weaver KE, Lesser GJ, Avis NE, Hundley WG. Changes in Physical Activity, Functional Capacity, and Cardiac Function during Breast Cancer Therapy. Cancer Epidemiol Biomarkers Prev. 2022 Jul 1;31(7):1509. doi: 10.1158/1055-9965.EPI-22-0470.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 18, 2021): 403
• Original Estimated Enrollment (submitted: May 31, 2016): 1000
• Estimated Study Completion Date: July 31, 2034
• Estimated Primary Completion Date: November 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria for Women with Stage I - III Breast Cancer:

• Stage I-III female breast cancer (including inflammatory and newly diagnosed or locally recurrent breast cancer) but not metastatic breast cancer being treated with curative intent
• > 18 years old
• Scheduled to receive chemotherapy and/or estrogen antagonist aromatase inhibitors (anastrozole [Arimidex], letrozole [Femara], exemestane [Aromasin]).
• Able to hold breath for 10 seconds
• ECOG performance status 0 -2
• Able to walk at least 2 blocks without chest pain, dyspnea, shortness of breath or fainting
• Able to exercise on a treadmill or stationary cycle
• Participants in other ongoing clinical trials are eligible for this study

Exclusion Criteria for Women with Stage I-III Breast Cancer:

• Those with ferromagnetic cerebral aneurysm clips or other intracranial metal; pacemakers, defibrillators, functioning neurostimulator devices or other implanted non-compatible MRI devices (patients with tissue expanders will not be excluded)
• If previously measured, known LVEF <50%
• Symptomatic claustrophobia
• Unable to provide informed consent
• At the beginning of the study, pregnant women and women who are breast-feeding will not be enrolled.
• Severe pulmonary hypertension

• Within the past 6 months:

  • Acute pulmonary embolus
  • Deep vein thrombosis

• Within the past month:

  • Heart attack
  • Unstable or stable angina (cardiac chest pain)
  • Left main coronary artery disease
  • Symptomatic heart failure
  • Uncontrolled hypertension (SBP > 180 mm Hg or DBP > 120 mm Hg)
  • Severe valvular heart disease
  • Uncontrolled metabolic disease (diabetes with fasting BS >300 mg/dl, thyrotoxicosis, myxedema)
  • Aortic aneurism (>45 mm diameter) or aortic dissection
  • Uncontrolled slow or fast heart rhythm causing symptoms or hemodynamic compromise
  • Hypertrophic obstructive cardiomyopathy
• Patient does not understand English

Inclusion Criteria for Women Free of Cancer for Comparison:

• Healthy female without known coronary artery disease > 18 years old
• Able to hold breath 10 seconds
• ECOG performance status = 0 or 1
• Able to walk at least 2 blocks without chest pain, dyspnea, shortness of breath or fainting
• Able to exercise on a treadmill or stationary cycle
• No personal history of cancer other than superficial skin cancers
• Has never received chemotherapy, radiation therapy, immunotherapy, or had breast cancer related surgery
• If previously measured, LVEF ≥ 50%

Exclusion Criteria for Women Free of Cancer for Comparison:

• Inflammatory conditions such as lupus or inflammatory bowel disease
• Overt coronary artery disease or heart failure
• Those with ferromagnetic cerebral aneurysm clips or other intracranial metal; pacemakers, defibrillators, functioning neurostimulator devices or other implanted non-compatible MRI devices
• Symptomatic claustrophobia
• Unable to provide informed consent
• At the beginning of the study, pregnant women or women who are breast feeding will not be enrolled.
• Severe pulmonary hypertension

• Within the past 6 months:

  • Acute pulmonary embolus
  • Deep vein thrombosis

• Within the past month:

  • Heart attack
  • Unstable or stable angina (cardiac chest pain)
  • Left main coronary artery disease
  • Symptomatic heart failure
  • Uncontrolled hypertension (SBP > 180 mm Hg or DBP > 120 mm Hg)
  • Severe valvular heart disease
  • Uncontrolled metabolic disease (diabetes with fasting BS >300 mg/dl, thyrotoxicosis, myxedema)
  • Aortic aneurism (>45 mm diameter) or aortic dissection
  • Uncontrolled slow or fast heart rhythm causing symptoms or hemodynamic compromise
  • Hypertrophic obstructive cardiomyopathy
• Patient does not understand English

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02791581
• Other Study ID Numbers: IRB00045463; WF 97415 ( Other Identifier: Sponsor ); 1R01CA199167-01 ( U.S. NIH Grant/Contract ); NCI-2017-00386 ( Registry Identifier: NCI Trial Identifier ); NCI-2017-00386 ( Registry Identifier: NCI CTRP )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Wake Forest NCORP Research Base is committed to following the NIH Statement on Sharing Research Data (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html). As of July 2018, the WF NCORP RB signed an agreement with NCI to contribute de-identified data and data dictionaries from clinical trials conducted through our RB to the NCI NCTN/NCORP data archive within 6 months of primary and non-primary publications of phase II/III and phase III trials to https://nctn-data-archive.nci.nih.gov/. This will become the primary means for sharing raw data, and we will adhere to the guidelines spelled out in the NCTN/NCORP Data Archive Usage Guide. De-identified data from studies not covered by the agreement (e.g., phase II and observational studies) will be made available upon request. All data files will be de-identified. De-identification procedures will meet the HIPAA criteria as detailed in the Code of Federal Regulations, Part 45, Section 164.514.
• Time Frame: 6 months after publication for a 2 year duration
• Access Criteria: upon request to NCORP@wakehealth.edu

• Current Responsible Party: Wake Forest University Health Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Wake Forest University Health Sciences
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Gregory Hundley, MD; Wake Forest University Health Sciences

• PRS Account: Wake Forest University Health Sciences
• Verification Date: January 2024