CHI: Community Hospital Identification of High CV Risk Patients During Cancer Treatment

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02566109
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Actual Duration (Months): 19.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The overall of this proposal is to test in community hospitals the utility of a 10-min magnetic resonance imaging (MRI) scan protocol combined with proprietary image analysis algorithms for detecting early cardiovascular (CV) injury during receipt of chemotherapy for breast cancer (BrC) and lymphoma. This technology provides health-care delivery systems with a time-efficient method to identify those at risk of a future CV event so that prevention can be implemented to prolong survival and reduce morbidity in cancer survivors.

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

Detailed Description

While recent research indicates that conventional MRI, advanced echocardiography (global longitudinal strain and 3D) and serum biomarkers can detect CV injury early after receipt of Chemotherapy, these methods require lengthy and difficult examinations that are not routinely executed in community hospitals where the majority of patients with BrC & lymphoma are treated. Yet, 1-month deteriorations in traditional 45-min MRI measures are known to forecast 6-month subclinical deteriorations in left ventricular ejection fraction (LVEF) that are associated with CV events. At the same time, new observational data indicate therapy with HMG-CoA reductase inhibitors/statins administered early during receipt of Chemotherapy may prevent subsequent cardiac dysfunction and CV events. Our MRI fast scanning techniques remedy these community hospital implementation obstacles.

In this proposal, the investigators propose to test the utility of these fast scans within an existing funded randomized clinical trial R01HL118740 of generic atorvastatin that is researching methods to prevent cardiotoxicity in patients treated with Chemotherapy for BrC and lymphoma (taking advantage of significant existing clinical trial resources). This study allows us to address our over-arching goal: to determine the optimal implementation (alone or in combination with other tests) of our proprietary MRI processes for forecasting CV injury in patients treated with Chemotherapy in community hospitals through performance of a Phase II comparative effectiveness study within an ongoing clinical trial.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Community Hospital Identification of High CV Risk Patients During Cancer Treatment (CHI)
• Actual Study Start Date: Feb 25, 2016
• Actual Primary Completion Date: Oct 4, 2017
• Actual Study Completion Date: Oct 4, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: Fast MRI All patients who agree to participate in this study will have a 10 minute fast MRI scan and Baseline and 6 month time periods. The fast MRI will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.	Diagnostic Test: Fast MRI; The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.

Outcome Measures

Primary Outcome Measures

1. Left Ventricular Ejection Fraction (LVEF) at Baseline, 2 Month Using Fast MRI, and 6 Months [Baseline, 2 months, and 6 months]

   To compare baseline, 2-month (using Fast MRI), and 6 month measures in left ventricular (LV) ejection fraction

2. End Diastolic Volume (EDV) at Baseline, 2 Month, and 6 Months [Baseline, 2 months, and 6 months]

   To compare baseline, 2-month (using Fast MRI), and 6 month measures in end Diastolic Volume (EDV)

3. End Systolic Volume (ESV) at Baseline, 2 Month, and 6 Months [Baseline, 2 months, and 6 months]

   To compare baseline, 2-month (using Fast MRI), and 6 month measures in end Systolic Volume (ESV)

4. Pulse Wave Velocity (PWV) at Baseline and 6 Months [Baseline and 6 months]

   To compare baseline and 6 month measures in pulse wave velocity (PWV)

Secondary Outcome Measures

1. Left Ventricular Ejection Fraction (LVEF): Comparison of Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline [Baseline]

   To compare Magnetic Resonance Imaging (MRI) metric of Left Ventricular Ejection Fraction (LVEF) with Echocardiogram (ECHO) at baseline

2. End Diastolic Volume (EDV): Compare Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline [Baseline]

   To compare magnetic resonance imaging (MRI) metric of End Diastolic Volume (EDV) with echocardiogram (ECHO) at baseline

3. End Systolic Volume (ESV): Compare Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline [Baseline]

   To compare magnetic resonance imaging (MRI) metric of End Systolic Volume (ESV) with echocardiogram (ECHO) at baseline

Other Outcome Measures

1. Exploratory Algorithmic Modeling [Baseline to 6 months]

   To use exploratory algorithmic modeling to obtain optimal strategies for determining the combination of metrics (10-min MR, ECHO, serum biomarkers) at 2-months that predict the 6-month post Chemotherapy deteriorations in cardiovascular function.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Newly diagnosed Stage I-III breast cancer (including inflammatory and newly diagnosed recurrent breast cancer) or lymphoma with a > 2 year life expectancy

• Scheduled to receive chemotherapy with an Anthracycline (doxorubicin or epirubicin)

• = or > 21 years of age

• Prior cancers allowed if no evidence of disease

• ECOG 0 or 1

• Enrollment in NCI Protocol #: WF 98213. Patients must receive Fast MRI and 3D ECHO along with Baseline (98213) MRI prior to first chemotherapy treatment.

Exclusion Criteria:

• Patients with ferromagnetic cerebral aneurysm clips or other intraorbital/intracranial metal; pacemakers, defibrillators, functioning neurostimulator devices or other implanted electronic devices.

• Most breast tissue expanders are not allowed. (If uncertain, inform the MRI tech to confirm eligibility status.)

• Unable to provide informed consent

• Symptomatic Claustrophobia

• Pregnant or breasting feeding. Due to unknown risks and potential harm to the unborn fetus a negative serum pregnancy test within 10 days prior to registration is required in patients with child-bearing potential. For this reason patients of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence (not having sex), oral contraceptives, intrauterine device (IUD), DeProvera, tubal ligation, or vasectomy of the partner (with confirmed negative sperm counts) in a monogamous relationship (same partner). An acceptable, although less reliable method involves the careful use of condoms and spermicidal foam or gel and/or cervical cap or sponge prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest School of Medicine	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 28, 2016

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT02566109
• Other Study ID Numbers: IRB00032416; WF-01115
• First Posted: Oct 2, 2015
• Last Update Posted: May 8, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Study Results

Participant Flow

Arm/Group Title	Fast MRI
Arm/Group Description	All patients who agree to participate in this study will have a 10 minute fast MRI scan and Baseline and 6 month time periods. The fast MRI will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment. Fast MRI: The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.
Period Title: Overall Study
STARTED	6
COMPLETED	5
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Fast MRI
Arm/Group Description	All patients who agree to participate in this study will have a 10 minute fast MRI scan and Baseline and 6 month time periods. The fast MRI will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment. Fast MRI: The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.
Overall Participants	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.1 (15.3)
Sex: Female, Male (Count of Participants)
Female	5 83.3%
Male	1 16.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%
Not Hispanic or Latino	5 83.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	6 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Left Ventricular Ejection Fraction (LVEF) (percentage of fluid expelled) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of fluid expelled]	61.51 (5.45)
End Diastolic Volume (EDV) - Magnetic Resonance Imaging (MRI) (mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL]	134.90 (41.70)
End Systolic Volume (ESV) - Magnetic Resonance Imaging (MRI) (mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL]	52.23 (18.91)
Pulse Wave Velocity (PWV) - Magnetic Resonance Imaging (MRI) (meters/sec) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters/sec]	4.74 (1.75)
Left Ventricular Ejection Fraction (LVEF) - Echocardiogram (ECHO) (percentage of fluid expelled) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of fluid expelled]	54.17 (7.03)
End Diastolic Volume (EDV) - Echocardiogram (ECHO) (mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL]	100.08 (24.20)
End Systolic Volume (ESV) - Echocardiogram (ECHO) (mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL]	44.90 (9.16)

Outcome Measures

1. Primary Outcome

Title	Left Ventricular Ejection Fraction (LVEF) at Baseline, 2 Month Using Fast MRI, and 6 Months
Description	To compare baseline, 2-month (using Fast MRI), and 6 month measures in left ventricular (LV) ejection fraction
Time Frame	Baseline, 2 months, and 6 months

Outcome Measure Data

Analysis Population Description

Only 5 received MRI at baseline, 4 at 2 months using Fast MRI, and 3 at 6 months.

Arm/Group Title	Fast MRI
Arm/Group Description	All patients who agree to participate in this study will have a 10 minute fast MRI scan and Baseline and 6 month time periods. The fast MRI will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment. Fast MRI: The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.
Measure Participants	5
2 months FAST MRI	56.67 (4.71)
6 months	58.69 (3.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fast MRI
	Comments	Correlation between baseline and 2 months.
	Type of Statistical Test	Other
	Comments	Estimation of Pearson correlation
Statistical Test of Hypothesis	p-Value	0.6102
	Comments
	Method	Pearson Correlation Coefficient
	Comments
Method of Estimation	Estimation Parameter	Pearson Correlation Coefficient
	Estimated Value	-0.57472
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fast MRI
	Comments	Correlation between baseline and 6 months.
	Type of Statistical Test	Other
	Comments	Correlation
Statistical Test of Hypothesis	p-Value	0.8343
	Comments
	Method	Peason Correlation Coefficient
	Comments
Method of Estimation	Estimation Parameter	Pearson Correlation Coefficient
	Estimated Value	0.25733
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	End Diastolic Volume (EDV) at Baseline, 2 Month, and 6 Months
Description	To compare baseline, 2-month (using Fast MRI), and 6 month measures in end Diastolic Volume (EDV)
Time Frame	Baseline, 2 months, and 6 months

Outcome Measure Data

Analysis Population Description

Only 5 received MRI at baseline, 4 at 2 months using Fast MRI, and 3 at 6 months.

Arm/Group Title	Fast MRI
Arm/Group Description	All patients who agree to participate in this study will have a 10 minute fast MRI scan and Baseline and 6 month time periods. The fast MRI will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment. Fast MRI: The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.
Measure Participants	5
2 months FAST MRI	126.07 (32.36)
6 months	130.20 (44.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fast MRI
	Comments	Correlation between baseline and 2 months.
	Type of Statistical Test	Other
	Comments	Pearson Correlation Coefficient
Statistical Test of Hypothesis	p-Value	0.9395
	Comments
	Method	Pearson Correlation Coefficient
	Comments
Method of Estimation	Estimation Parameter	Pearson Correlation Coefficient
	Estimated Value	-0.09487
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fast MRI
	Comments	Correlation between baseline and 6 months.
	Type of Statistical Test	Other
	Comments	Pearson Correlation Coefficient
Statistical Test of Hypothesis	p-Value	0.1486
	Comments
	Method	Pearson Correlation Coefficient
	Comments
Method of Estimation	Estimation Parameter	Pearson Correlation Coefficient
	Estimated Value	0.97287
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	End Systolic Volume (ESV) at Baseline, 2 Month, and 6 Months
Description	To compare baseline, 2-month (using Fast MRI), and 6 month measures in end Systolic Volume (ESV)
Time Frame	Baseline, 2 months, and 6 months

Outcome Measure Data

Analysis Population Description

Only 5 received MRI at baseline, 4 at 2 months using Fast MRI, and 3 at 6 months.

Arm/Group Title	Fast MRI
Arm/Group Description	All patients who agree to participate in this study will have a 10 minute fast MRI scan and Baseline and 6 month time periods. The fast MRI will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment. Fast MRI: The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.
Measure Participants	5
2 months FAST MRI	54.72 (14.52)
6 months	54.73 (23.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fast MRI
	Comments	Correlation between baseline and 2 months.
	Type of Statistical Test	Other
	Comments	Pearson Correlation Coefficient
Statistical Test of Hypothesis	p-Value	0.9341
	Comments
	Method	Pearson Correlation Coefficient
	Comments
Method of Estimation	Estimation Parameter	Pearson Correlation Coefficient
	Estimated Value	0.10327
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fast MRI
	Comments	Correlation between baseline and 6 months.
	Type of Statistical Test	Other
	Comments	Pearson Correlation Coefficient
Statistical Test of Hypothesis	p-Value	0.0497
	Comments
	Method	Pearson Correlation Coefficient
	Comments
Method of Estimation	Estimation Parameter	Pearson Correlation Coefficient
	Estimated Value	0.99696
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Pulse Wave Velocity (PWV) at Baseline and 6 Months
Description	To compare baseline and 6 month measures in pulse wave velocity (PWV)
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

Only 5 received MRI at baseline and 3 at 6 months.

Arm/Group Title	Fast MRI
Arm/Group Description	All patients who agree to participate in this study will have a 10 minute fast MRI scan and Baseline and 6 month time periods. The fast MRI will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment. Fast MRI: The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.
Measure Participants	5
Baseline	4.74 (1.75)
6 months	4.07 (1.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fast MRI
	Comments
	Type of Statistical Test	Other
	Comments	Pearson Correlation Coefficient
Statistical Test of Hypothesis	p-Value	0.1129
	Comments
	Method	Pearson Correlation Coefficient
	Comments
Method of Estimation	Estimation Parameter	Pearson Correlation Coefficient
	Estimated Value	0.98432
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Left Ventricular Ejection Fraction (LVEF): Comparison of Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline
Description	To compare Magnetic Resonance Imaging (MRI) metric of Left Ventricular Ejection Fraction (LVEF) with Echocardiogram (ECHO) at baseline
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

All 6 participants that received both an ECHO. Only 5 had an MRI at baseline

Arm/Group Title	Fast MRI
Arm/Group Description	All patients who agree to participate in this study will have a 10 minute fast MRI scan and Baseline and 6 month time periods. The fast MRI will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment. Fast MRI: The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.
Measure Participants	6
LVEF Echo	54.17 (7.03)
LVEF MRI	61.51 (5.45)

6. Secondary Outcome

Title	End Diastolic Volume (EDV): Compare Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline
Description	To compare magnetic resonance imaging (MRI) metric of End Diastolic Volume (EDV) with echocardiogram (ECHO) at baseline
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

All 6 participants that received both an ECHO. Only 5 had an MRI at baseline

Arm/Group Title	Fast MRI
Arm/Group Description	All patients who agree to participate in this study will have a 10 minute fast MRI scan and Baseline and 6 month time periods. The fast MRI will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment. Fast MRI: The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.
Measure Participants	6
EDV Echo	100.08 (24.20)
EDV MRI	134.90 (41.70)

7. Secondary Outcome

Title	End Systolic Volume (ESV): Compare Magnetic Resonance Imaging (MRI) With Echocardiogram (ECHO) at Baseline
Description	To compare magnetic resonance imaging (MRI) metric of End Systolic Volume (ESV) with echocardiogram (ECHO) at baseline
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

All 6 participants that received both an ECHO. Only 5 had an MRI at baseline

Arm/Group Title	Fast MRI
Arm/Group Description	All patients who agree to participate in this study will have a 10 minute fast MRI scan and Baseline and 6 month time periods. The fast MRI will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment. Fast MRI: The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.
Measure Participants	6
ESV Echo	44.90 (9.16)
ESV MRI	52.23 (18.91)

8. Other Pre-specified Outcome

Title	Exploratory Algorithmic Modeling
Description	To use exploratory algorithmic modeling to obtain optimal strategies for determining the combination of metrics (10-min MR, ECHO, serum biomarkers) at 2-months that predict the 6-month post Chemotherapy deteriorations in cardiovascular function.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From time of signed informed consent to 30 days post study completion for each participant. Study completion was approximately 6 months.
Adverse Event Reporting Description	Grades 1, 2, and 3 expected (solicited) and unexpected (unsolicited) adverse events (AE)s that meet the above definition for an AE and are only definitely related, possibly related or probably related to this study intervention should be reported using the Toxicity Assessment Sheet. Hospitalizations that are scheduled for routine treatments and procedures unrelated to study intervention do not need to be reported. All toxicities are graded using CTCAE v4.03.
Arm/Group Title	Fast MRI
Arm/Group Description	All patients who agree to participate in this study will have a 10 minute fast MRI scan and Baseline and 6 month time periods. The fast MRI will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment. Fast MRI: The fast MRI is a 10 minute MRI scan that will be used to determine if cardiovascular injury can be detected early while patients are receiving chemotherapy treatment.
All Cause Mortality
	Fast MRI
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Serious Adverse Events
	Fast MRI
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Fast MRI
	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)
Infections and infestations
Febrile neutropenia	1/6 (16.7%)	1
Nervous system disorders
Headache	1/6 (16.7%)	1

Limitations/Caveats

Early termination leading to small number of subject analyzed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.