UPBEAT: Understanding and Predicting Breast Cancer Events After Treatment

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02791581

Collaborator

National Cancer Institute (NCI) (NIH)

403

Enrollment

Locations

Arms

204.3

Anticipated Duration (Months)

6.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Diagnostic Test: Cardiac MRI	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

403 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Understanding and Predicting Breast Cancer Events After Treatment (UPBEAT)

Actual Study Start Date :

Jul 21, 2017

Anticipated Primary Completion Date :

Jul 31, 2023

Anticipated Study Completion Date :

Jul 31, 2034

Arms and Interventions

Arm	Intervention/Treatment
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.	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.
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.	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.

Arm

Intervention/Treatment

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.

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.

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.

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.

Outcome Measures

Primary Outcome Measures

FACT-Fatigue [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 [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 [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 [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 [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 [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.

Secondary Outcome Measures

Cohen's 4-item Perceived Stress Scale (PSS) [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 [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 [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 [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) [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) [Baseline, 3 months, 12 months and 24 months]
Screening questionnaire assessing depressive symptoms during the last week
Godin Leisure-Time Exercise Questionnaire (LTEQ) [Baseline, 3 months, 12 months and 24 months]
Main process measure of physical activity participation
PACE Adult Sedentary Behaviors Survey [Baseline, 3 months, 12 months and 24 months]
Assess sedentary lifestyle behaviors
PROMIS Short Form 8A Measure of Sleep Disturbance [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 [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 [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 [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 [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 [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 [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 [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 [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.

Other Outcome Measures

B-type natriuretic peptide (BNP) [Baseline and 24 months]
Serum BNP as a predictor of exercise intolerance
Troponin - 1 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
3	Moffitt Cancer Center - McKinley Campus	Tampa	Florida	United States	33612
4	Moffitt Cancer Center	Tampa	Florida	United States	33612
5	Northwestern University	Chicago	Illinois	United States	60611
6	IU Health North Hospital	Carmel	Indiana	United States	46032
7	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
8	Springmill Medical Center	Indianapolis	Indiana	United States	46290
9	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
10	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas	United States	66205
11	Tufts Medical Center	Boston	Massachusetts	United States	02111
12	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
13	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
14	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan	United States	48336
15	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
16	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
17	William Beaumont Hospital - Troy	Troy	Michigan	United States	48085
18	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
19	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
20	Health Partners Inc	Minneapolis	Minnesota	United States	55454
21	Regions Hospital	Saint Paul	Minnesota	United States	55101
22	United Hospital	Saint Paul	Minnesota	United States	55102
23	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
24	Morristown Medical Center	Morristown	New Jersey	United States	07960
25	Newton Medical Center	Newton	New Jersey	United States	07860
26	Overlook Hospital	Summit	New Jersey	United States	07902
27	Randolph Hospital	Asheboro	North Carolina	United States	27203
28	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina	United States	27215
29	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
30	Duke University Medical Center	Durham	North Carolina	United States	27710
31	Cone Health Cancer Center	Greensboro	North Carolina	United States	27403
32	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
33	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania	United States	17109
34	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
35	UPMC Memorial	York	Pennsylvania	United States	17408
36	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina	United States	29316
37	Prisma Health Cancer Institute - Easley	Easley	South Carolina	United States	29640
38	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina	United States	29605
39	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
40	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
41	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
42	Prisma Health Cancer Institute - Greer	Greer	South Carolina	United States	29650
43	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
44	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
45	Centra Lynchburg Hematology-Oncology Clinic Inc	Lynchburg	Virginia	United States	24501
46	Virginia Cancer Institute	Richmond	Virginia	United States	23230
47	VCU Massey Cancer Center at Stony Point	Richmond	Virginia	United States	23235
48	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
49	Shenandoah Oncology PC	Winchester	Virginia	United States	22601
50	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
51	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
52	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin	United States	54937
53	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
54	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
55	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
56	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
57	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin	United States	53209
58	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
59	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
60	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
61	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
62	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
63	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
64	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
65	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
66	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227

Sponsors and Collaborators

Wake Forest University Health Sciences
National Cancer Institute (NCI)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Wake Forest University Health Sciences

ClinicalTrials.gov Identifier:

NCT02791581

Other Study ID Numbers:

IRB00045463
WF 97415
1R01CA199167-01
NCI-2017-00386
NCI-2017-00386

First Posted:

Jun 7, 2016

Last Update Posted:

Aug 23, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Yes

Keywords provided by Wake Forest University Health Sciences

Breast Cancer

Fatigue

Cardiovascular Events

Additional relevant MeSH terms:

Breast Neoplasms

Study Results

No Results Posted as of Aug 23, 2022