Ultrasound and Near Infrared Imaging for Predicting and Monitoring Neoadjuvant Treatment

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT02891681
• Collaborator: National Institute for Biomedical Imaging and Bioengineering (NIBIB) (NIH)
• Enrollment: 41
• Location: 1
• Arms: 2
• Actual Duration (Months): 37.8
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

To determine the accuracy of NIR/US assessment of tumor vasculature and oxygen changes in predicting and monitoring early neoadjuvant treatment response compared to pathological response.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Breast Tumors; Cancer of Breast; Cancer of the Breast; Malignant Neoplasm of Breast	Device: Optical Tomography Using Near Infrared Diffused Light Assisted with Ultrasound	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Ultrasound and Near Infrared Imaging for Predicting and Monitoring Neoadjuvant Treatment
• Actual Study Start Date: Nov 29, 2016
• Actual Primary Completion Date: Jan 23, 2020
• Actual Study Completion Date: Jan 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NIR/US (Neoadjuvant Chemotherapy Cohort) Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, end of cycle 5 (only if treatment regimen changed), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen	Device: Optical Tomography Using Near Infrared Diffused Light Assisted with Ultrasound; Other Names: NIR/US
Experimental: NIR/US (Neoadjuvant Endocrine Cohort) Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, at time of treatment regimen change (only intended for those who have had a change in their regimen), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen	Device: Optical Tomography Using Near Infrared Diffused Light Assisted with Ultrasound; Other Names: NIR/US

Outcome Measures

Primary Outcome Measures

1. Pathologic Response Based on Miller-Payne Grading System [Up to 6 months]

   In the Miller-Payne system, the pathologic response is divided into 5 grades based on comparison of tumor cellularity between pre-neoadjuvant core biopsy and definitive surgical specimen as: grade 1: no change or some alteration to individual malignant cells but no reduction in overall cellularity (pNR) grade 2: a minor loss of tumor cells but overall cellularity still high; up to 30% (pPR) grade 3: between an estimated 30% and 90% reduction in tumor cells (pPR) grade 4: a marked disappearance of tumor cells such that only small clusters or widely dispersed individual cells remain (almost pCR); more than 90% loss of tumor cells grade 5: no malignant cells identifiable in sections from the site of the tumor; only vascular fibroelastonic stroma remains often containing macrophages (pCR) (however, ductal carcinoma in situ (DCIS) may be present)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Scheduled to receive neoadjuvant chemotherapy for the treatment of newly diagnosed, locally advanced breast cancer or scheduled to receive neoadjuvant endocrine therapy with the eventual goal of surgery of newly diagnosed clinical stage II-III ER+ HER2- breast cancer (for the endocrine therapy cohort)

• At least 18 years of age

• Female

• Able to understand and willing to sign an IRB-approved written informed consent document

Exclusion Criteria:

• Pregnant and/or breastfeeding

• Prior history of breast cancer

• Prior history of chest wall radiation

• Prior history of breast reconstruction, reduction, or augmentation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Investigators

• Principal Investigator: Quing Zhu, Ph.D., Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 10, 2020
• Informed Consent Form - Mar 25, 2020

More Information

Additional Information:

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT02891681
• Other Study ID Numbers: 201608101; 7R01EB002136-12
• First Posted: Sep 7, 2016
• Last Update Posted: Feb 16, 2021
• Last Verified: Jan 1, 2021

• 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
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Neoplasms; Breast Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	An additional arm (NIR/US - Crossover from Endocrine Cohort to Chemotherapy Cohort) was added for results reporting as one participant transitioned from the Endocrine Cohort to the Chemotherapy Cohort because the participant's therapy was changed mid-treatment from Endocrine to Chemotherapy.

Arm/Group Title	NIR/US (Neoadjuvant Chemotherapy Cohort)	NIR/US (Neoadjuvant Endocrine Cohort)	NIR/US (Crossover From Endocrine Cohort to Chemotherapy Cohort)
Arm/Group Description	Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, end of cycle 5 (only if treatment regimen changed), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen	Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, at time of treatment regimen change (only intended for those who have had a change in their regimen), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen	Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, at time of treatment regimen change (only intended for those who have had a change in their regimen), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen
Period Title: Overall Study
STARTED	39	1	1
COMPLETED	36	1	0
NOT COMPLETED	3	0	1

Baseline Characteristics

Arm/Group Title	NIR/US (Neoadjuvant Chemotherapy Cohort)	NIR/US (Neoadjuvant Endocrine Cohort)	NIR/US (Crossover From Endocrine Cohort to Chemotherapy Cohort)	Total
Arm/Group Description	Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, end of cycle 5 (only if treatment regimen changed), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen	Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, at time of treatment regimen change (only intended for those who have had a change in their regimen), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen	Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, at time of treatment regimen change (only intended for those who have had a change in their regimen), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen	Total of all reporting groups
Overall Participants	39	1	1	41
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	45	66	53	45
Sex: Female, Male (Count of Participants)
Female	39 100%	1 100%	1 100%	41 100%
Male	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.6%	0 0%	0 0%	1 2.4%
Not Hispanic or Latino	38 97.4%	1 100%	1 100%	40 97.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	8 20.5%	1 100%	1 100%	10 24.4%
White	31 79.5%	0 0%	0 0%	31 75.6%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	39 100%	1 100%	1 100%	41 100%

Outcome Measures

1. Primary Outcome

Title	Pathologic Response Based on Miller-Payne Grading System
Description	In the Miller-Payne system, the pathologic response is divided into 5 grades based on comparison of tumor cellularity between pre-neoadjuvant core biopsy and definitive surgical specimen as: grade 1: no change or some alteration to individual malignant cells but no reduction in overall cellularity (pNR) grade 2: a minor loss of tumor cells but overall cellularity still high; up to 30% (pPR) grade 3: between an estimated 30% and 90% reduction in tumor cells (pPR) grade 4: a marked disappearance of tumor cells such that only small clusters or widely dispersed individual cells remain (almost pCR); more than 90% loss of tumor cells grade 5: no malignant cells identifiable in sections from the site of the tumor; only vascular fibroelastonic stroma remains often containing macrophages (pCR) (however, ductal carcinoma in situ (DCIS) may be present)
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

For this outcome measure, the one participant who was in the crossover cohort was counted in the neoadjuvant chemotherapy cohort. Three participants in the neoadjuvant chemotherapy cohort were not evaluable for this outcome measure (2 developed metastases prior to completing neoadjuvant therapy and 1 was taken off study after first imaging appointment).

Arm/Group Title	NIR/US (Neoadjuvant Chemotherapy Cohort)	NIR/US (Neoadjuvant Endocrine Cohort)	NIR/US (Crossover From Endocrine Cohort to Chemotherapy Cohort)
Arm/Group Description	Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, end of cycle 5 (only if treatment regimen changed), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen	Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, at time of treatment regimen change (only intended for those who have had a change in their regimen), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen	Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, at time of treatment regimen change (only intended for those who have had a change in their regimen), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen
Measure Participants	37	1	0
Grade 1	4 10.3%	1 100%
Grade 2	3 7.7%	0 0%
Grade 3	8 20.5%	0 0%
Grade 4	3 7.7%	0 0%
Grade 5	19 48.7%	0 0%

Adverse Events

Time Frame	Serious adverse events that occurred within 24 hours of the NIR/US were collected and reported, assessed up to 6 months (~6 months)
Adverse Event Reporting Description	Adverse events were not collected for this study. If a serious adverse event was suspected to be caused by the NIR/US scan then it was collected and reported.
Arm/Group Title	NIR/US (Neoadjuvant Chemotherapy Cohort)		NIR/US (Neoadjuvant Endocrine Cohort)		NIR/US (Crossover From Endocrine Cohort to Chemotherapy Cohort)
Arm/Group Description	Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, end of cycle 5 (only if treatment regimen changed), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen		Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, at time of treatment regimen change (only intended for those who have had a change in their regimen), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen		Patients will have the NIR/US baseline scan performed before their first treatment. The desirable schedule will be >= 7 days after initial biopsy to avoid confounding effects from the biopsy related acute inflammatory response. In addition, patients will also have NIR/US performed at end of cycle 1, end of cycle 2, end of cycle 3, at time of treatment regimen change (only intended for those who have had a change in their regimen), and prior to surgery. The number of NIR/US study visits may vary (5-6) depending on the patient's treatment regimen
All Cause Mortality
	NIR/US (Neoadjuvant Chemotherapy Cohort)		NIR/US (Neoadjuvant Endocrine Cohort)		NIR/US (Crossover From Endocrine Cohort to Chemotherapy Cohort)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/1 (0%)		0/1 (0%)
Serious Adverse Events
	NIR/US (Neoadjuvant Chemotherapy Cohort)		NIR/US (Neoadjuvant Endocrine Cohort)		NIR/US (Crossover From Endocrine Cohort to Chemotherapy Cohort)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	NIR/US (Neoadjuvant Chemotherapy Cohort)		NIR/US (Neoadjuvant Endocrine Cohort)		NIR/US (Crossover From Endocrine Cohort to Chemotherapy Cohort)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

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.