Breast Cancer
Conditions
Brief summary
This is a non-randomized, open-label, multi-site study to collect safety and efficacy data on an intraoperative imaging system, the LUM Imaging System (LUM015 imaging agent in conjunction with the LUM imaging device), in identifying residual cancer in the tumor bed of female breast cancer patients. During the study, study physicians and clinical staff will complete hands-on training in anticipation of the upcoming pivotal study. Site-specific or user-specific issues related to the use of the device will be identified and addressed. Additionally, the data collected in the study will be used to continue training the tumor detection algorithm of the device. In this study, patients will be injected with LUM015 prior to surgery. The study physicians will perform lumpectomy procedures according to his or her institution's standard of care practice. After the main specimen removal is completed, the study physician will use the LUM Imaging Device to image the tumor bed. Therapeutic shaves will be removed based on the recommendation of the LUM Imaging System. Patients will be followed until their first standard of care post-operative follow-up visit.
Detailed description
For breast cancer lumpectomies, the presence of residual cancer cells left in the tumor bed after initial resection in inferred by post-operative margin assessment of the resected tissue by a pathologist. Phase C enrollment will include approximately 5 patients per surgeon, with 2-3 surgeons per site and up to 20 sites. Subjects undergoing a lumpectomy procedure to treat primary breast cancer will be injected with a single dose of LUM015 4 ± 2 hours prior to surgery at a dose of 1.0 mg/kg. The sequence of events during the surgical procedure will vary based on the standard of care used by the surgeon. Patients will receive at a minimum the standard of care practices for each site. Lumicell-guided shaved cavity margins will be removed after the surgeon has attempted to remove the main specimen with grossly negative margins. Study treatment ends when the surgery is completed. All patients will continue their enrollment in the study until their first follow-up visit and they will continue to be followed until the medical team determines no further surgical intervention is required. Patients with adverse events that are determined to be possibly related to the LUM Imaging System will be followed until resolution or stabilization of the adverse event.
Interventions
COMBINATION_PRODUCTLUM Imaging System
Drug: LUM015 Device: LUM 2.6 Imaging Device
Sponsors
National Cancer Institute (NCI)
Lumicell, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must have histologically or cytologically confirmed primary invasive breast cancer, ductal carcinoma in situ (DCIS) or a combination of invasive breast cancer and DCIS. The protocol accepted methods for obtaining the histological samples are diagnostic core needle biopsies or fine needle biopsies. * Female, age of 18 years or older. Because no dosing or adverse event data are currently available on the use of LUM015 in subjects \<18 years of age, children are excluded from this study. * Subjects must be scheduled for a lumpectomy for a breast malignancy. * Subjects must be able and willing to follow study procedures and instructions. * Subjects must have received and signed an informed consent form. * Subjects must have no uncontrolled serious medical problems except for the diagnosis of cancer, as per the
Exclusion criteria
listed below. * Subjects must have normal organ and marrow function within limits as defined below: * Leukocytes \> 3,000/mcL * Platelets \> 75,000/mcL * total bilirubin within normal institutional limits * AST (SGOT)/ALT (SGPT) \< 2.5 X institutional upper limit of normal * Creatinine ≤ 1.5 mg/dL or creatinine clearance \> 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Collect Data to Refine and Verify the Tumor Detection Algorithm. | 1 day | Data were collected from mITT population, which included all the patients imaged with the LUM Imaging System. This metric measured the residual cancer that current Standard of Care (SOC) lumpectomy failed to remove. It was defined as among all the patients, the percentage of subjects who had residual cancer found in at least one LUM-guided shave (therapeutic shave or T-shave) after the current initial SOC lumpectomy procedure was completed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Reported Adverse Events | Patients were evaluated for adverse events from time of injection until standard post-surgery follow-up visit (Median 31 days after lumpectomy). | Reported adverse events will be assessed and aggregated according to event type, relation to device or drug, and severity. |
| Tumor Removal Rate in the Whole mITT Population by SOC Margin Status | 1 week | Collect data to verify the detection algorithm reported in previous studies by SOC margin status |
| Tumor Removal Rate Within Subjects Having Positive Standard of Care Margins | 1 Week | Tumor removal rate was measured as the percentage of the subjects who had residual tumor removed guided by Lumicell Imaging System after standard of care (SOC) procedure within subjects who had positive margins after SOC. |
| Tumor Removal Rate Within Subjects Having All Negative SOC Margins | 1 Week | Tumor removal rate was measured as the percentage of the subjects who had residual tumor removed guided by Lumicell Imaging System after standard of care (SOC) procedure within subjects who had negative margins after SOC. |
| Detection and Conversion of Positive Margins in Subjects After BCS SOC | 1 Week | Conversion was measured as the ratio of the subjects having all the positive margins after BCS SOC converted to negatives after Lumicell Imaging guided procedure. Detection was measured as the ratio of the subjects having all or at least one positive margin after BCS SOC detected by Lumicell Imaging System. BCS: Breast-conserving surgery; SOC: Standard of Care |
| Volume of Therapeutic Shaves Removed During Lumpectomy. | 1 Week | The median volumes of Lumicell Imaging System - guided shaves (therapeutic shaves) were measured and the median total volume removed during lumpectomy was presented as well. |
| Contribution of Therapeutic Shaves to Total Volume Removed During Lumpectomy. | 1 Week | The contribution of the volumes of Lumicell Imaging System - guided shaves (therapeutic shaves) were measured as percentage of the sum of the volumes of the therapeutic shaves out of the total volume removed during lumpectomy. |
| Sensitivity and Specificity of the LUM Imaging System in Predicting Residual Cancer in the Cavity | 1 Week | Sensitivity and specificity were measured at the tissue level for the Lumicell imaging signal for the sensitivity and specificity on the residual tumor in the cavity of corresponding orientations after standard of care (SOC) of Lumpectomy. Generalized Estimating Equation (GEE) has been applied using generalized linear model having binomial link function and compound symmetry working correlation structure within each subject. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Surgeons Trained on the Use of the LUM Imaging System | 1 day | Surgeons were trained on using the LUM Imaging System in preparation for participating in future clinical trials with the LUM Imaging System. Workflows were established at each institution to support the use of the LUM Imaging System and protocol adherence during lumpectomy procedures. Surgeons were not participants in the trial. Surgeons were the Investigators in the trial. |
Countries
United States
Participant flow
Recruitment details
Per protocol, the enrolled population are those who were injected with LUM015.
Participants by arm
| Arm | Count |
|---|---|
| LUM Imaging System Single dose of LUM015 (1.0 mg/kg) will be administered by intravenous injection between 2 to 6 hours prior to surgery. All subjects undergo lumpectomy as standard of care and will have the study intervention, guidance by intraoperative imaging using the LUM Imaging Device | 234 |
| Total | 234 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawn prior to LUM Imaging Procedure completed | 4 |
Baseline characteristics
| Characteristic | LUM Imaging System |
|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 9.8 |
| Body Mass Index | 29.0 Kg/m^2 STANDARD_DEVIATION 6.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 220 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants |
| Mammographic breast density Almost entirely fatty | 12 Participants |
| Mammographic breast density Extremely dense | 11 Participants |
| Mammographic breast density Heterogeneously dense | 86 Participants |
| Mammographic breast density Scattered areas of fibroglandular density | 119 Participants |
| Mammographic breast density Unknown | 6 Participants |
| Menopausal Status Post-menopausal | 187 Participants |
| Menopausal Status Pre/Peri-menopausal | 47 Participants |
| Palpability Not palpable mass | 171 Participants |
| Palpability Palpable mass | 63 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) White | 187 Participants |
| Region of Enrollment United States | 234 participants |
| Sex: Female, Male Female | 234 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 234 |
| other Total, other adverse events | 215 / 234 |
| serious Total, serious adverse events | 1 / 234 |
Outcome results
Primary
Collect Data to Refine and Verify the Tumor Detection Algorithm.
Data were collected from mITT population, which included all the patients imaged with the LUM Imaging System. This metric measured the residual cancer that current Standard of Care (SOC) lumpectomy failed to remove. It was defined as among all the patients, the percentage of subjects who had residual cancer found in at least one LUM-guided shave (therapeutic shave or T-shave) after the current initial SOC lumpectomy procedure was completed.
Time frame: 1 day
Population: modified intent to treat population (mITT) includes subjects injected with LUM015 and LUM Imaging was performed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LUM Imaging System | Collect Data to Refine and Verify the Tumor Detection Algorithm. | 11.3 Percentage |
Secondary
Contribution of Therapeutic Shaves to Total Volume Removed During Lumpectomy.
The contribution of the volumes of Lumicell Imaging System - guided shaves (therapeutic shaves) were measured as percentage of the sum of the volumes of the therapeutic shaves out of the total volume removed during lumpectomy.
Time frame: 1 Week
Population: Total mITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LUM Imaging System | Contribution of Therapeutic Shaves to Total Volume Removed During Lumpectomy. | 6.5 Percentage |
Secondary
Detection and Conversion of Positive Margins in Subjects After BCS SOC
Conversion was measured as the ratio of the subjects having all the positive margins after BCS SOC converted to negatives after Lumicell Imaging guided procedure. Detection was measured as the ratio of the subjects having all or at least one positive margin after BCS SOC detected by Lumicell Imaging System. BCS: Breast-conserving surgery; SOC: Standard of Care
Time frame: 1 Week
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LUM Imaging System | Detection and Conversion of Positive Margins in Subjects After BCS SOC | Percentage of Subjects Having SOC Positive Margins All Converted to Negative | 15.8 Percentage of All Subjects |
| LUM Imaging System | Detection and Conversion of Positive Margins in Subjects After BCS SOC | Percentage of Subjects Having SOC Positive Margins All Detected by Lumicell Device | 28.9 Percentage of All Subjects |
| LUM Imaging System | Detection and Conversion of Positive Margins in Subjects After BCS SOC | Percentage of Subjects Having At Least One SOC Positive Margin Detected by Lumicell Device | 42.1 Percentage of All Subjects |
Secondary
Number of Patients With Reported Adverse Events
Reported adverse events will be assessed and aggregated according to event type, relation to device or drug, and severity.
Time frame: Patients were evaluated for adverse events from time of injection until standard post-surgery follow-up visit (Median 31 days after lumpectomy).
Population: Subjects injected with LUM015 at a dose of 1mg/kg.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| LUM Imaging System | Number of Patients With Reported Adverse Events | Chromaturia Adverse Events | Mild or Moderate, Related | 214 Participants |
| LUM Imaging System | Number of Patients With Reported Adverse Events | Chromaturia Adverse Events | Mild or Moderate, Not Related | 0 Participants |
| LUM Imaging System | Number of Patients With Reported Adverse Events | Chromaturia Adverse Events | Severe, Not Related | 0 Participants |
| LUM Imaging System | Number of Patients With Reported Adverse Events | Chromaturia Adverse Events | Severe, Related | 0 Participants |
| LUM Imaging System | Number of Patients With Reported Adverse Events | Chromaturia Adverse Events | Life Threatening, Not Related | 0 Participants |
| LUM Imaging System | Number of Patients With Reported Adverse Events | Chromaturia Adverse Events | Life Threatening, Related | 0 Participants |
| LUM Imaging System | Number of Patients With Reported Adverse Events | Non Chromaturia Adverse Events | Mild or Moderate, Not Related | 33 Participants |
| LUM Imaging System | Number of Patients With Reported Adverse Events | Non Chromaturia Adverse Events | Mild or Moderate, Related | 1 Participants |
| LUM Imaging System | Number of Patients With Reported Adverse Events | Non Chromaturia Adverse Events | Severe, Not Related | 0 Participants |
| LUM Imaging System | Number of Patients With Reported Adverse Events | Non Chromaturia Adverse Events | Severe, Related | 1 Participants |
| LUM Imaging System | Number of Patients With Reported Adverse Events | Non Chromaturia Adverse Events | Life Threatening, Not Related | 0 Participants |
| LUM Imaging System | Number of Patients With Reported Adverse Events | Non Chromaturia Adverse Events | Life Threatening, Related | 1 Participants |
Secondary
Sensitivity and Specificity of the LUM Imaging System in Predicting Residual Cancer in the Cavity
Sensitivity and specificity were measured at the tissue level for the Lumicell imaging signal for the sensitivity and specificity on the residual tumor in the cavity of corresponding orientations after standard of care (SOC) of Lumpectomy. Generalized Estimating Equation (GEE) has been applied using generalized linear model having binomial link function and compound symmetry working correlation structure within each subject.
Time frame: 1 Week
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LUM Imaging System | Sensitivity and Specificity of the LUM Imaging System in Predicting Residual Cancer in the Cavity | Sensitivity (GEE) | 69.3 Percentage |
| LUM Imaging System | Sensitivity and Specificity of the LUM Imaging System in Predicting Residual Cancer in the Cavity | Specificity (GEE) | 71.7 Percentage |
Secondary
Tumor Removal Rate in the Whole mITT Population by SOC Margin Status
Collect data to verify the detection algorithm reported in previous studies by SOC margin status
Time frame: 1 week
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LUM Imaging System | Tumor Removal Rate in the Whole mITT Population by SOC Margin Status | Percentage of subjects with positive SOC margins having tumor in at least one therapeutic shave. | 5.2 Percentage of All Subjects |
| LUM Imaging System | Tumor Removal Rate in the Whole mITT Population by SOC Margin Status | Percentage of subjects with negative SOC margins having tumor in at least one therapeutic shave. | 6.1 Percentage of All Subjects |
Secondary
Tumor Removal Rate Within Subjects Having All Negative SOC Margins
Tumor removal rate was measured as the percentage of the subjects who had residual tumor removed guided by Lumicell Imaging System after standard of care (SOC) procedure within subjects who had negative margins after SOC.
Time frame: 1 Week
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LUM Imaging System | Tumor Removal Rate Within Subjects Having All Negative SOC Margins | 7.3 Percentage of Subjects |
Secondary
Tumor Removal Rate Within Subjects Having Positive Standard of Care Margins
Tumor removal rate was measured as the percentage of the subjects who had residual tumor removed guided by Lumicell Imaging System after standard of care (SOC) procedure within subjects who had positive margins after SOC.
Time frame: 1 Week
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LUM Imaging System | Tumor Removal Rate Within Subjects Having Positive Standard of Care Margins | 31.6 Percentage of Subjects |
Secondary
Volume of Therapeutic Shaves Removed During Lumpectomy.
The median volumes of Lumicell Imaging System - guided shaves (therapeutic shaves) were measured and the median total volume removed during lumpectomy was presented as well.
Time frame: 1 Week
Population: Total mITT population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LUM Imaging System | Volume of Therapeutic Shaves Removed During Lumpectomy. | Lumpectomy volume (cm3) | 57.8 Volume in CM^3 |
| LUM Imaging System | Volume of Therapeutic Shaves Removed During Lumpectomy. | SOC shave volume (cm3) | 6.0 Volume in CM^3 |
| LUM Imaging System | Volume of Therapeutic Shaves Removed During Lumpectomy. | SOC total volume (cm3) | 65.4 Volume in CM^3 |
| LUM Imaging System | Volume of Therapeutic Shaves Removed During Lumpectomy. | Therapeutic shave volume (cm3) | 4.0 Volume in CM^3 |
| LUM Imaging System | Volume of Therapeutic Shaves Removed During Lumpectomy. | Total volume (cm3) | 77.7 Volume in CM^3 |
Other Pre-specified
Number of Surgeons Trained on the Use of the LUM Imaging System
Surgeons were trained on using the LUM Imaging System in preparation for participating in future clinical trials with the LUM Imaging System. Workflows were established at each institution to support the use of the LUM Imaging System and protocol adherence during lumpectomy procedures. Surgeons were not participants in the trial. Surgeons were the Investigators in the trial.
Time frame: 1 day
Population: Thirty-eight surgeons at 16 clinical sites were trained on the use of the LUM Imaging System.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LUM Imaging System | Number of Surgeons Trained on the Use of the LUM Imaging System | 38 Participants |