Imagio Feasibility Multi-Reader, Multi-Case Study

• Sponsor: Seno Medical Instruments Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03708393
• Collaborator: American College of Radiology (Other)
• Enrollment: 155
• Location: 1
• Arms: 2
• Actual Duration (Days): 26
• Patients Per Site Per Month: 181.5

Study Details

Study Description

Brief Summary

Controlled, blinded, multi-reader, multi-case study

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Device: Imagio (IUS+OA); Device: Imagio Ultrasound; Device: Mammography	N/A

Detailed Description

The Imagio Feasibility Reader Study-01 Study is intended to evaluate if a subsequent pivotal study can be implemented to test prospective hypotheses for pre-specified effectiveness endpoints with an acceptable sample size. The Feasibility Study will be based on ITD masses from the PIONEER (NCT01943916) Pivotal study to simultaneously reflect the distributions with and without mammograms as well as site CDU BI-RADS scores within benign and malignant masses as strata. The study population will be split into 3 cohorts - Cohort 1, the 120 patient ITD Population used to run the primary/ secondary analyses. Cohort 2, 30 patients used to run exploratory analyses on false negative rate and Cohort 3, 5 patients used to run exploratory analyses on specific mass types

Study Design

• Study Type: Interventional
• Actual Enrollment: 155 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: This will be a controlled, blinded, multi-reader, multi-case (MRMC) study using a sequential design. The study will include 5-12 independent readers depending on qualifications and availability. Imagio (IUS+OA) Training to be completed prior to any reads taking place. Read 1 is immediately followed by Read 2 within the same read session. Read 1 (Control): Mammogram (if available) + History + IUS (stills and videos provided), IUS Probability of Malignancy (POM) and BI-RADS scored and the data form locked. Read 2 (Test): Mammogram (if available) + History + IUS (stills and videos provided), and Imagio (IUS+OA) (stills and videos provided). An interim IUS POM and BI-RADS is recorded as well as a combined Imagio (IUS+OA) POM and BIRADS Pre and Post SenoGram on separate data forms.This will be a controlled, blinded, multi-reader, multi-case (MRMC) study using a sequential design. The study will include 5-12 independent readers depending on qualifications and availability. Imagio (IUS+OA) Training to be completed prior to any reads taking place. Read 1 is immediately followed by Read 2 within the same read session. Read 1 (Control): Mammogram (if available) + History + IUS (stills and videos provided), IUS Probability of Malignancy (POM) and BI-RADS scored and the data form locked. Read 2 (Test): Mammogram (if available) + History + IUS (stills and videos provided), and Imagio (IUS+OA) (stills and videos provided). An interim IUS POM and BI-RADS is recorded as well as a combined Imagio (IUS+OA) POM and BIRADS Pre and Post SenoGram on separate data forms.
• Masking: Single (Outcomes Assessor)
• Masking Description: Independent Readers blinded to mass diagnosis
• Primary Purpose: Diagnostic
• Official Title: Imagio Feasibility Multi-Reader, Multi-Case Study of Optoacoustic Images Versus Imagio Ultrasound to Guide Decision to Biopsy
• Actual Study Start Date: Nov 13, 2018
• Actual Primary Completion Date: Dec 9, 2018
• Actual Study Completion Date: Dec 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Imagio IUS Read 1 - Mammo (as available) + Imagio Ultrasound	Device: Imagio Ultrasound; Imagio ultrasound images to be reviewed as part of the reader study; Device: Mammography; Mammography images as available per standard of care; Other Names: Mammo
Experimental: Imagio (IUS+OA) Read 2 - Mammo (as available) + (Imagio Ultrasound + OA)	Device: Imagio (IUS+OA); The Imagio ultrasound and opto-acoustic images to be reviewed as part of the reader study; Device: Mammography; Mammography images as available per standard of care; Other Names: Mammo

Outcome Measures

Primary Outcome Measures

1. The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 [Baseline to 12 month follow-up]

   Primary effectiveness endpoint was the specificity of Imagio [IUS+OA] compared to IUS alone at fixed 95-99% sensitivity (fSp) interpolated from the area under the curve (AUC) of receiver operating characteristic (ROC) curves, averaged across all 10 independent readers. Both imaging modalities (IUS alone and IUS+OA) were read for each subject (subject as own control). Results for each imaging modality compared to biopsy diagnosis or 12-month follow-up ruling of benign as determined by truth panel (ground truth).

Secondary Outcome Measures

1. Partial Receiver Operating Characteristic (ROC) Area Under the Curve (pAUC), Cohort 1 [Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months (≥11 months)]

   pAUC considers only the region of the ROC space that corresponds to clinically relevant values of sensitivity defined as 95% to 99% for Imagio [IUS+OA] vs. IUS alone; averaged across 10 readers.

2. BiRads [Breast Imaging Reporting and Data System] Downgrades and Upgrades- Cohort 1 [Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months]

   The cumulative effect of downgrades and upgrades for benign masses expressed as the net gain of True Negative reads

3. The Negative Likelihood Ratio (NLR) for IUS vs. Imagio® (IUS+OA), Cohort 1 [Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months (≥11 months)]

   NLR (Imagio [IUS+OA] vs. IUS alone); averaged across 10 readers (all readers).

4. SenoGram Usage Cohort 1 for Imagio (IUS+OA) Only [Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months]

   SenoGram Utilization by number of readers using the SenoGram reported by the readers. SenoGram is not used for Imagio IUS Arm only Imagio (IUS+OA)

5. SenoGram Performance [Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months]

   Sensitivity of SenoGram estimated from cross-validation - Cohort 1

6. SenoGram Performance [Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months]

   Specificity of SenoGram estimated from cross-validation

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Female subjects participating in the PIONEER-0 Study of the Imagio Breast Imaging System with known clinical status

Exclusion Criteria:

• Female subjects who did not have known clinical status in the PIONEER-0 Study of the Imagio Breast Imaging System with known clinical status

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	American College of Radiology	Philadelphia	Pennsylvania	United States	19103

Sponsors and Collaborators

• Seno Medical Instruments Inc.
• American College of Radiology

Investigators

• Study Director: A. Thomas Stavros, MD, Seno Medical

Study Documents (Full-Text)

• Study Protocol - Nov 1, 2018
• Statistical Analysis Plan - Nov 9, 2018

More Information

Publications

None provided.

• Responsible Party: Seno Medical Instruments Inc.
• ClinicalTrials.gov Identifier: NCT03708393
• Other Study ID Numbers: Reader-01
• First Posted: Oct 17, 2018
• Last Update Posted: Aug 6, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• 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.: Yes

Study Results

Participant Flow

Recruitment Details

New Independent Reader Feasibility Study (new readers re-reading a sub-set of randomly selected images acquired during PIONEER-01 Study (NCT01943916); Reader-01 study execution dates: 13 Nov 2018 to 6 Dec 2018

Pre-assignment Detail

Breast mass images were acquired during PIONEER-01 study. The Reader-01 study-single arm, sequentially read (IUS vs. Imagio [IUS+OA]), controlled, blinded, multi-reader, multi-case (MRMC) feasibility study. New readers recruited; NO new subjects were recruited. Subject baseline, demographic and safety data comes from PIONEER-01 subjects who were randomly selected for Reader-01 study. Outcome measures compared IUS vs. IUS+OA. Truth based on biopsy diagnosis or 12 Mo F/U truth panel decision.

Arm/Group Title	Overall (Subjects Randomly Selected From PIONEER-01 Study)
Arm/Group Description	Each subject in all 3 cohorts had one mass that was read by all readers. Each subject served as her own control, with imaging of each mass by both IUS and IUS+OA modalities. All subjects for all 3 cohorts were included in safety analysis. All subjects for all 3 cohorts were followed and completed in the same manner. Cohort 1 (n=120 was representative of the subject population for the primary analysis, Cohort 2 (n=30) was special population for internal study of FN's and Cohort 3 (n=5) was for internal study of DCIS masses.
Period Title: Overall Study
STARTED	155
COMPLETED	155
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Overall (Subjects Randomly Selected From PIONEER-01 Study)
Arm/Group Description	Each subject had one mass that was read by all readers. Each subject served as her own control, with imaging of each mass by both IUS and IUS+OA modalities. Therefore, baseline data are for overall population only.
Overall Participants	155
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51.2 (14.5)
Sex: Female, Male (Count of Participants)
Female	155 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	24 15.5%
Not Hispanic or Latino	130 83.9%
Unknown or Not Reported	1 0.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	7 4.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	24 15.5%
White	117 75.5%
More than one race	1 0.6%
Unknown or Not Reported	6 3.9%
Region of Enrollment (Count of Participants)
United States	155 100%
Mass Diagnosis (Count of Participants)
Subjects: Benign (includes benign + Truth Panel Benign [TPB]) (Cohort 1)	75 48.4%
Subjects: Malignant (Cohort 1)	45 29%
Subjects: Malignant false negative in PIONEER-01 (Cohort 2)	30 19.4%
Subjects: Malignant atypical (Cohort 3)	5 3.2%

Outcome Measures

1. Primary Outcome

Title	The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1
Description	Primary effectiveness endpoint was the specificity of Imagio [IUS+OA] compared to IUS alone at fixed 95-99% sensitivity (fSp) interpolated from the area under the curve (AUC) of receiver operating characteristic (ROC) curves, averaged across all 10 independent readers. Both imaging modalities (IUS alone and IUS+OA) were read for each subject (subject as own control). Results for each imaging modality compared to biopsy diagnosis or 12-month follow-up ruling of benign as determined by truth panel (ground truth).
Time Frame	Baseline to 12 month follow-up

Outcome Measure Data

Analysis Population Description

120 patients/masses were included in Cohort 1-the Intent-to-diagnose (ITD) population used to run the analysis to set the sample size for the future pivotal Reader-02 Study, 30 masses Cohort 2 to assess False negative rate, and 5 Cohort 3 DCIS, lymphoma, etc. masses to assess how readers scored. 155 masses in total across all cohorts analyzed for the Safety population analysis

Arm/Group Title	IUS Alone	Imagio (IUS+OA)
Arm/Group Description	IUS alone imaging	IUS+OA imaging
Measure Participants	120	120
fSp (95.0%)	80.9	75.4
fSp (96.0%)	78.7	71.4
fSp (97.0%)	75.8	66.1
fSp (97.5%)	74	62.8
fSp (98.0%)	71.8	58.9
fSp (99.0%)	65.2	47.7

2. Secondary Outcome

Title	Partial Receiver Operating Characteristic (ROC) Area Under the Curve (pAUC), Cohort 1
Description	pAUC considers only the region of the ROC space that corresponds to clinically relevant values of sensitivity defined as 95% to 99% for Imagio [IUS+OA] vs. IUS alone; averaged across 10 readers.
Time Frame	Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months (≥11 months)

Outcome Measure Data

Analysis Population Description

Cohort 1, pAUC considers only the region of the ROC space that corresponds to clinically relevant values of sensitivity defined as 95% to 99% for Imagio [IUS+OA] vs. IUS alone; averaged across 10 readers.

Arm/Group Title	Imagio IUS	Imagio (IUS+OA)
Arm/Group Description	Read 1 - Mammo (as available) + Imagio Ultrasound Imagio Ultrasound: Imagio ultrasound images to be reviewed as part of the reader study Mammography: Mammography images as available per standard of care	Read 2 - Mammo (as available) + (Imagio Ultrasound + OA) Imagio (IUS+OA): The Imagio ultrasound and opto-acoustic images to be reviewed as part of the reader study Mammography: Mammography images as available per standard of care
Measure Participants	120	120
Mean (95% Confidence Interval) [Probability as percentage]	2.6	3.0

3. Secondary Outcome

Title	BiRads [Breast Imaging Reporting and Data System] Downgrades and Upgrades- Cohort 1
Description	The cumulative effect of downgrades and upgrades for benign masses expressed as the net gain of True Negative reads
Time Frame	Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months

Outcome Measure Data

Analysis Population Description

ITD Population- Number of Subjects/Masses 120

Arm/Group Title	Imagio IUS	Imagio (IUS+OA)
Arm/Group Description	Read 1 - Mammo (as available) + Imagio Ultrasound Imagio Ultrasound: Imagio ultrasound images to be reviewed as part of the reader study Mammography: Mammography images as available per standard of care	Read 2 - Mammo (as available) + (Imagio Ultrasound + OA) Imagio (IUS+OA): The Imagio ultrasound and opto-acoustic images to be reviewed as part of the reader study Mammography: Mammography images as available per standard of care
Measure Participants	120	120
Number [% of correctly identified benign masses]	38.5	49.1

4. Secondary Outcome

Title	The Negative Likelihood Ratio (NLR) for IUS vs. Imagio® (IUS+OA), Cohort 1
Description	NLR (Imagio [IUS+OA] vs. IUS alone); averaged across 10 readers (all readers).
Time Frame	Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months (≥11 months)

Outcome Measure Data

Analysis Population Description

Cohort 1 - 120

Arm/Group Title	IUS Alone	Imagio (IUS+OA)
Arm/Group Description	Results for IUS alone readings	IUS+OA imaging Results for Imagio readings
Measure Participants	120	120
Mean (99% Confidence Interval) [Ratio]	.049	.094

5. Secondary Outcome

Title	SenoGram Usage Cohort 1 for Imagio (IUS+OA) Only
Description	SenoGram Utilization by number of readers using the SenoGram reported by the readers. SenoGram is not used for Imagio IUS Arm only Imagio (IUS+OA)
Time Frame	Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months

Outcome Measure Data

Analysis Population Description

Cohort 1

Arm/Group Title	Imagio IUS	Imagio (IUS+OA)
Arm/Group Description	Read 1 - Mammo (as available) + Imagio Ultrasound Imagio Ultrasound: Imagio ultrasound images to be reviewed as part of the reader study Mammography: Mammography images as available per standard of care	Read 2 - Mammo (as available) + (Imagio Ultrasound + OA) Imagio (IUS+OA): The Imagio ultrasound and opto-acoustic images to be reviewed as part of the reader study Mammography: Mammography images as available per standard of care
Measure Participants	120	120
Number [participants]	NA NaN	111 NaN

6. Secondary Outcome

Title	SenoGram Performance
Description	Sensitivity of SenoGram estimated from cross-validation - Cohort 1
Time Frame	Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months

Outcome Measure Data

Analysis Population Description

ITD Population

Arm/Group Title	Imagio IUS	Imagio (IUS+OA)
Arm/Group Description	Read 1 - Mammo (as available) + Imagio Ultrasound Imagio Ultrasound: Imagio ultrasound images to be reviewed as part of the reader study Mammography: Mammography images as available per standard of care	Read 2 - Mammo (as available) + (Imagio Ultrasound + OA) Imagio (IUS+OA): The Imagio ultrasound and opto-acoustic images to be reviewed as part of the reader study Mammography: Mammography images as available per standard of care
Measure Participants	120	120
Number [Percent]	NA	98.0

7. Secondary Outcome

Title	SenoGram Performance
Description	Specificity of SenoGram estimated from cross-validation
Time Frame	Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months

Outcome Measure Data

Analysis Population Description

ITD Population - Cohort 1

Arm/Group Title	IUS Alone	Imagio (IUS+OA)
Arm/Group Description	Results for IUS alone readings	IUS+OA imaging Results for Imagio readings
Measure Participants	120	120
Number [Percent]	NA	62.2

Adverse Events

Time Frame	Baseline to 12 months +/- 30 days follow-up. Adverse Events were recorded from the use of the Imagio during the original PIONEER Study and reported out for those participants/masses selected for the Reader-01 Independent Reader Study.
Arm/Group Title	Overall (Masses Randomly Selected From PIONEER-01 Study)
Arm/Group Description	Each subject had one mass that was read by all readers. Each subject served as her own control, with imaging of each mass by both IUS and IUS+OA modalities. Therefore, safety data are for overall population only.
All Cause Mortality
	Overall (Masses Randomly Selected From PIONEER-01 Study)
	Affected / at Risk (%)	# Events
Total	0/155 (0%)
Serious Adverse Events
	Overall (Masses Randomly Selected From PIONEER-01 Study)
	Affected / at Risk (%)	# Events
Total	0/155 (0%)
Other (Not Including Serious) Adverse Events
	Overall (Masses Randomly Selected From PIONEER-01 Study)
	Affected / at Risk (%)	# Events
Total	0/155 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS 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.