Breast Cancer
Conditions
Brief summary
The Imagio® Pivotal Study is intended to evaluate if the results observed in the previous Feasibility Study can be confirmed for pre-specified effectiveness endpoints. Using Intention-to-Diagnose (ITD) masses from the PIONEER Pivotal study, 480 to 840 masses are to be used for the Pivotal Study, the remaining masses will be reserved for training the SenoGram® model.
Detailed description
This will be a controlled, blinded, multi-reader, multi-case (MRMC) study using a sequential design. The study will include 15 readers with an additional 5 as back-up readers depending on qualifications and availability. Readers that participated in the Seno PIONEER Study (NCT01943916) or the Reader-01 Feasibility Study (NCT03708393) are not eligible to participate as readers in this Pivotal Study. Imagio® \[Ultrasound (IUS) + Optoacoustic (OA)\] (IUS)(IUS+OA) training will be completed prior to any reads taking place. Read 1 will be immediately followed by Read 2 within the same read session.
Interventions
DEVICEReader Study - Imagio Ultrasound
Imagio ultrasound images to be reviewed as part of Reader study
DEVICEReader Study Imagio Ultrasound + Optoacoustic Imaging
Imagio Ultrasound + Optoacoustic images to be reviewed as part of Reader study
DEVICEMammography
Mammography as available per standard of care
Sponsors
Seno Medical Instruments Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Masking description
Readers will not be provided with information regarding the initial patient diagnosis
Intervention model description
This will be a controlled, blinded, multi-reader, multi-case (MRMC) study using a sequential design. The study will include 15 readers with an additional 5 as back-up readers depending on qualifications and availability. Readers that participated in the Seno PIONEER Study or the Reader-01 Feasibility Study are not eligible to participate as readers in this Pivotal Study.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* One analyzable mass per patient: BI-RADS 3 and 4a, 4b, 4c and 5 masses as declared by clinical site investigator via PIONEER study inclusion criteria and categorized as BIRADS 3, 4a, 4b 4c and 5 by conventional diagnostic ultrasound (CDU) * Masses declared to be in the PIONEER Intention to Diagnose (ITD)/analysis population, including high risk cases per original PIONEER protocol * Patient age, indication for study entry and available medical history * Evaluable mammograms and OA and IUS video loops and stills for each mass
Exclusion criteria
* Critical missing IUS or OA still image and/or video loop views or incorrect IUS or OA stills and video loops that would preclude a case from being evaluated by readers * Reader-02 Proficiency Test and training cases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gain in Specificity at Fixed 98% Sensitivity (fSp) | Baseline to 12 months +/- 30 days follow-up | Primary effectiveness endpoint was the difference (gain) in specificity (fSp) at fixed 98% sensitivity for the Imagio IUS+OA relative to IUS alone, across all 15 independent readers; both imaging modalities used in 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). fSp derived from empirical receiver operating characteristic (ROC) using endpoint interpolation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Negative Likelihood Ratio (NLR) | Baseline to 12 months +/- 30 days follow-up | NLR for the Imagio IUS+OA relative to IUS alone, across all 15 independent readers; both imaging modalities used in 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). NLR = \[(1-sensitivity) / specificity\]. |
| Positive Likelihood Ratio (PLR) | Baseline to 12 months +/- 30 days follow-up | PLR for the Imagio IUS+OA relative to IUS alone, across all 15 independent readers; both imaging modalities used in 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). PLR = \[sensitivity / (1-specificity)\]. |
| Partial Area Under the Curve (pAUC) | Baseline to 12 months +/- 30 days follow-up | pAUC considers only the region of the area under the ROC curve that corresponds to clinically relevant values of sensitivity, defined as 95% to 100%, for Imagio IUS+OA vs. IUS alone, averaged across 15 readers. Both imaging modalities used in 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). A higher pAUC indicates better diagnostic accuracy. |
Countries
United States
Participant flow
Recruitment details
New Independent Reader Study (new readers re-reading a sub-set of randomly selected images acquired during PIONEER-01 Study- (NCT01943916)). Reader-02 study execution dates: 30 Jul 2019 to 3 Nov 2019
Pre-assignment details
Imagio Ultrasound (IUS) and Imagio optoacoustic/ultrasound (IUS+OA) images of breast masses previously acquired from the PIONEER-01 study (NCT01943916) referenced above were used for this study. Reader-02 was a single-arm sequentially read multi reader/case (MRMC) study comparing IUS vs Imagio (IUS+OA). New readers were recruited-NO new subjects/masses. Results were based on biopsy diagnosis or truth panel decision as ground truth obtained during PIONEER-01.
Participants by arm
| Arm | Count |
|---|---|
| Overall (Subjects Randomly Selected From PIONEER-01 Study) 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 derived from PIONEER-01 for sub set of 480 cases read during Reader-02 Study. | 480 |
| Total | 480 |
Baseline characteristics
| Characteristic | Overall (Subjects Randomly Selected From PIONEER-01 Study) |
|---|---|
| Age, Continuous | 49.9 Years STANDARD_DEVIATION 14.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 87 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 387 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Mass Diagnosis Subjects (Benign+TPB+HR) | 300 Participants |
| Mass Diagnosis Subjects (Cancer) | 180 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 14 Participants |
| Race (NIH/OMB) Black or African American | 54 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 20 Participants |
| Race (NIH/OMB) White | 389 Participants |
| Region of Enrollment United States | 480 Participants |
| Sex: Female, Male Female | 480 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 480 |
| other Total, other adverse events | 14 / 480 |
| serious Total, serious adverse events | 2 / 480 |
Outcome results
Primary
Gain in Specificity at Fixed 98% Sensitivity (fSp)
Primary effectiveness endpoint was the difference (gain) in specificity (fSp) at fixed 98% sensitivity for the Imagio IUS+OA relative to IUS alone, across all 15 independent readers; both imaging modalities used in 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). fSp derived from empirical receiver operating characteristic (ROC) using endpoint interpolation.
Time frame: Baseline to 12 months +/- 30 days follow-up
Population: Intent-to-diagnose (ITD)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IUS Alone | Gain in Specificity at Fixed 98% Sensitivity (fSp) | 38.22 % benign+TPB masses correctly identified |
| Imagio (IUS+OA) | Gain in Specificity at Fixed 98% Sensitivity (fSp) | 47.20 % benign+TPB masses correctly identified |
p-value: 0.0268Random Reader, Random Mass
Secondary
Negative Likelihood Ratio (NLR)
NLR for the Imagio IUS+OA relative to IUS alone, across all 15 independent readers; both imaging modalities used in 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). NLR = \[(1-sensitivity) / specificity\].
Time frame: Baseline to 12 months +/- 30 days follow-up
Population: Intent-to-diagnose (ITD)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IUS Alone | Negative Likelihood Ratio (NLR) | 0.053 Ratio |
| Imagio (IUS+OA) | Negative Likelihood Ratio (NLR) | 0.047 Ratio |
Secondary
Partial Area Under the Curve (pAUC)
pAUC considers only the region of the area under the ROC curve that corresponds to clinically relevant values of sensitivity, defined as 95% to 100%, for Imagio IUS+OA vs. IUS alone, averaged across 15 readers. Both imaging modalities used in 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). A higher pAUC indicates better diagnostic accuracy.
Time frame: Baseline to 12 months +/- 30 days follow-up
Population: Intent-to-diagnose (ITD)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IUS Alone | Partial Area Under the Curve (pAUC) | 0.0205 Percentage of Probability |
| Imagio (IUS+OA) | Partial Area Under the Curve (pAUC) | 0.0244 Percentage of Probability |
Secondary
Positive Likelihood Ratio (PLR)
PLR for the Imagio IUS+OA relative to IUS alone, across all 15 independent readers; both imaging modalities used in 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). PLR = \[sensitivity / (1-specificity)\].
Time frame: Baseline to 12 months +/- 30 days follow-up
Population: Total population of subjects/masses
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IUS Alone | Positive Likelihood Ratio (PLR) | 1.548 Ratio |
| Imagio (IUS+OA) | Positive Likelihood Ratio (PLR) | 1.959 Ratio |