Breast Cancer
Conditions
Brief summary
For most breast cancer patients, surgery is the primary treatment. When patients undergo a lumpectomy, it is difficult for the surgeon to determine the extent of the tumor which results in incomplete tumor removal as determined by a positive margin assessment several days after the initial surgery is completed. Most patients with positive margins will undergo a second or even a third surgery to complete the tumor removal. The investigators hypothesize that the LUM Imaging System can reduce the rates of positive margins and, thus, the rates of second surgeries by identifying microscopic residual cancer in the tumor bed. This is a non-randomized, open label study to evaluate the safety and efficacy of an intraoperative imaging system, the LUM Imaging System (LUM015 in conjunction with LUM 2.6 Imaging Device), in identifying residual cancer in the tumor bed of female breast cancer subjects. The study is composed of a Feasibility Trial divided into two phases: Phase A (15 total subjects) and Phase B (up to 50 total subjects). During Phase A, 15 subjects will be evaluated to collect additional patient safety data, select the dose of LUM015 for Phase B and evaluate the device function. During Phase B, subjects will be injected with LUM015 at the dose determined during Phase A to preliminarily assess the performance of the detection algorithm against pathology margin assessment. In Phase B, the surgeon will perform standard of care surgery and then use the LUM Imaging System to guide the removal of additional cavity shavings as indicated by the LUM Imaging System.
Detailed description
The LUM Imaging System consists of the cancer imaging agent LUM015 and a hand-held fluorescence-based imager that collects the emission of activated LUM015 in and around tumor. The LUM Imaging System is designed to detect microscopic residual cancer cells in real-time within the tumor bed. In this study, we will evaluate the performance of the LUM Imaging System in detecting residual cancer and guiding its removal during lumpectomies. In Phase A, all patients will receive standard of care surgery followed by intraoperative imaging of the tumor bed and resected tissue with the LUM 2.6 Imaging Device. In Phase A, no clinical decisions are made based on the imaging results. Standard of care margin assessment will be performed and compared against the imaging results with the LUM Imaging System. Subjects in Phase B will receive standard of care surgery followed by intraoperative imaging of the tumor bed with the LUM Imaging System. In Phase B, the surgeon will remove an additional shaved margin specimen if indicated by the LUM Imaging System. Final margin assessment will be performed on the very last shaved margin specimen removed. All participating subjects will be observed to collect safety data from the time of injection of LUM015 to the time the clinical team decides no additional surgery is needed.
Interventions
DRUGLUM015
DEVICELUM 2.6 Imaging Device
Sponsors
National Cancer Institute (NCI)
Massachusetts General Hospital
Dana-Farber Cancer Institute
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
* Histologically or cytologically confirmed primary breast cancer. * Female, age of 18 years or older. * Scheduled for a lumpectomy of a breast tumor. * Able and willing to follow study procedures and instructions. * Subjects must have received and signed an informed consent form. * Subjects must be otherwise healthy except for the diagnosis of cancer, as per the
Exclusion criteria
listed below. * Subjects must have normal organ and marrow function as defined below: * Leukocytes \> 3,000/mcL * Absolute neutrophil count \> 1,500/mcL * Platelets \> 100,000/mcL * total bilirubin within normal institutional limits * AST (SGOT)/ALT (SGPT) \< 2.5 X institutional upper limit of normal * Creatinine within normal institutional limits or creatinine clearance \> 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal. * Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) starting the day entering the study, and for 60 days after injection of the imaging agent. * Subjects with ECOG performance status of 0 or 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| (Phase A Only) Selection of Dose of LUM015 to be Used in Future Breast Trials | 1 day | tumor-to-normal tissue signal ratio as a function of dose of LUM015 |
| (Phase B Only)Sensitivity and Specificity of the Lumicell Imaging System for Detecting Cancer | 1 day | Data from the participants in Phase A was used to develop an initial tumor detection algorithm that was then tested in Phase B. Thus, this endpoint is only applicable to the participants enrolled in the Phase B portion of the study. This endpoint measures the ability of the system to detect cancer as measured by sensitivity and specificity as defined below: Sensitivity = \[number of true positives/(number of true positives + number of false negatives)\] x 100% Specificity = \[number of true negatives/(number of true negatives + number of false positives)\] x 100% True positives = positive signal from imaging system and cancer found in tissue by pathology False positives = positive signal from imaging system and no cancer found in tissue by pathology True negatives = negative signal from imaging system and no cancer found in tissue by pathology False negatives = negative signal from imaging system and cancer found in tissue by pathology |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events as a Measure of Safety of the LUM Imaging System in Breast Cancer Subjects. | Patients were evaluated for adverse events from time of injection until standard post-surgery follow-up visit. (Median 31 days after lumpectomy). | Serious Adverse Events: Include adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Non-Serious Adverse Events: Adverse events that are not Serious Adverse Events. |
Countries
United States
Participant flow
Recruitment details
Phase A enrolled 15 women undergoing lumpectomy for primary breast cancers assigned sequentially to one of the 3 different dose arms (no dose of LUM015, 0.5mg/kg of LUM015, and 1.0mg/kg of LUM015). Phase B patients enrolled until 10 patients had positive margins in their standard of care cavity shave or a maximum of 50 patients was reached, whichever happened first.
Participants by arm
| Arm | Count |
|---|---|
| Phase A: No Dose 5 participants were not administered with LLUM015 All participants will have intraoperative imaging using the LUM 2.6 Imaging Device. | 5 |
| Phase A: LUM015 0.5 mg/kg 5 participants were administered with LLUM015 at 0.5 mg/kg by intravenous injection between 2 to 6 hours prior to surgery.
All participants will have intraoperative imaging using the LUM 2.6 Imaging Device. | 5 |
| Phase A: LUM015 1.0 mg/kg 5 participants were administered with LLUM015 at 1.0 mg/kg by intravenous injection between 2 to 6 hours prior to surgery.
All participants will have intraoperative imaging using the LUM 2.6 Imaging Device. | 5 |
| Phase B: LUM015 1.0 mg/kg 45 participants were administered with a single dose of LUM015 at 1.0mg/kg by intravenous injection between 2 and 6 hours prior to surgery. Patients will then undergo lumpectomy followed by LUM imagining of the lumpectomy cavity. Comprehensive shaves will be performed followed by LUM015 imagining of the resulting cavity and resection of LUM-imagining-positive cavity tissue. | 45 |
| Total | 60 |
Baseline characteristics
| Characteristic | Phase A: No Dose | Phase A: LUM015 0.5 mg/kg | Total | Phase B: LUM015 1.0 mg/kg | Phase A: LUM015 1.0 mg/kg |
|---|---|---|---|---|---|
| Age, Continuous | 69 years | 65 years | 60 years | 60 years | 59 years |
| Cancer Histologic Type (from surgical excision) Invasive Ductal Carcinoma and Invasive Lobular Carcinoma with or without Ductal Carcinoma In Situ | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Cancer Histologic Type (from surgical excision) Invasive Ductal Carcinoma with or without Ductal Carcinoma In Situ | 2 Participants | 4 Participants | 36 Participants | 27 Participants | 3 Participants |
| Cancer Histologic Type (from surgical excision) Invasive Lobular Carcinoma with or without Ductal Carcinoma In Situ | 1 Participants | 0 Participants | 7 Participants | 6 Participants | 0 Participants |
| Cancer Histologic Type (from surgical excision) No Tumor Found | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Cancer Histologic Type (from surgical excision) Pure Ductal Carcinoma In Situ | 2 Participants | 1 Participants | 13 Participants | 9 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 54 Participants | 39 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 6 Participants | 6 Participants | 0 Participants |
| Invasive Tumor Size in Largest Dimension | 1 cm | 1.85 cm | 1.2 cm | 1.2 cm | 1.6 cm |
| Mammographic Breast Density Almost Entirely Fatty | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants |
| Mammographic Breast Density Extremely Dense | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Mammographic Breast Density Heterogeneously Dense | 2 Participants | 3 Participants | 31 Participants | 22 Participants | 4 Participants |
| Mammographic Breast Density Mixed Scattered Fibroglandular/Heterogeneously Dense | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Mammographic Breast Density Scattered Areas of Fibroglandular/Heterogeneously Dense | 2 Participants | 1 Participants | 21 Participants | 18 Participants | 0 Participants |
| Menopausal Status Post-menopause | 5 Participants | 4 Participants | 27 Participants | 14 Participants | 4 Participants |
| Menopausal Status Pre/Peri-menopause | 0 Participants | 1 Participants | 33 Participants | 31 Participants | 1 Participants |
| Patients with Node Positive Disease | 0 Participants | 0 Participants | 7 Participants | 6 Participants | 1 Participants |
| Physical Examination Findings No Palpable Mass | 4 Participants | 4 Participants | 44 Participants | 32 Participants | 4 Participants |
| Physical Examination Findings Palpable Mass | 1 Participants | 1 Participants | 16 Participants | 13 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 5 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 53 Participants | 38 Participants | 5 Participants |
| Region of Enrollment United States | 5 participants | 5 participants | 60 participants | 45 participants | 5 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 60 Participants | 45 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Tumor Receptors All Triple Her-2, ER, PR Negatives | 0 Participants | 0 Participants | 5 Participants | 4 Participants | 1 Participants |
| Tumor Receptors All Triple Her-2, ER, PR Neither triple negative nor triple positive | 4 Participants | 3 Participants | 29 Participants | 19 Participants | 3 Participants |
| Tumor Receptors All Triple Her-2, ER, PR Positives | 1 Participants | 2 Participants | 4 Participants | 0 Participants | 1 Participants |
| Tumor Receptors Estrogen Receptor (ER) Negatives | 0 Participants | 0 Participants | 6 Participants | 5 Participants | 1 Participants |
| Tumor Receptors Estrogen Receptor (ER) Neither triple negative nor triple positive | NA Participants | NA Participants | NA Participants | NA Participants | NA Participants |
| Tumor Receptors Estrogen Receptor (ER) Positives | 5 Participants | 5 Participants | 33 Participants | 19 Participants | 4 Participants |
| Tumor Receptors Her-2 Negatives | 3 Participants | 2 Participants | 30 Participants | 22 Participants | 3 Participants |
| Tumor Receptors Her-2 Neither triple negative nor triple positive | NA Participants | NA Participants | NA Participants | NA Participants | NA Participants |
| Tumor Receptors Her-2 Positives | 1 Participants | 2 Participants | 12 Participants | 8 Participants | 1 Participants |
| Tumor Receptors Progesterone Receptor (PR) Negatives | 0 Participants | 0 Participants | 8 Participants | 7 Participants | 1 Participants |
| Tumor Receptors Progesterone Receptor (PR) Neither triple negative nor triple positive | NA Participants | NA Participants | NA Participants | NA Participants | NA Participants |
| Tumor Receptors Progesterone Receptor (PR) Positives | 5 Participants | 5 Participants | 31 Participants | 17 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 45 |
| other Total, other adverse events | 0 / 5 | 0 / 5 | 0 / 5 | 5 / 45 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 45 |
Outcome results
Primary
(Phase A Only) Selection of Dose of LUM015 to be Used in Future Breast Trials
tumor-to-normal tissue signal ratio as a function of dose of LUM015
Time frame: 1 day
Population: 5 patients not injected with LUM015, 5 patients injected with LUM015 at 0.5 mg/kg, and 5 patients injected with LUM015 at 1.0 mg/kg.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase A No LUM015 | (Phase A Only) Selection of Dose of LUM015 to be Used in Future Breast Trials | 2.1 Ratio | Standard Deviation 0.7 |
| Phase A 0.5 mg/kg | (Phase A Only) Selection of Dose of LUM015 to be Used in Future Breast Trials | 4.7 Ratio | Standard Deviation 2 |
| Phase A 1.0 mg/kg | (Phase A Only) Selection of Dose of LUM015 to be Used in Future Breast Trials | 4.2 Ratio | Standard Deviation 2.1 |
Primary
(Phase B Only)Sensitivity and Specificity of the Lumicell Imaging System for Detecting Cancer
Data from the participants in Phase A was used to develop an initial tumor detection algorithm that was then tested in Phase B. Thus, this endpoint is only applicable to the participants enrolled in the Phase B portion of the study. This endpoint measures the ability of the system to detect cancer as measured by sensitivity and specificity as defined below: Sensitivity = \[number of true positives/(number of true positives + number of false negatives)\] x 100% Specificity = \[number of true negatives/(number of true negatives + number of false positives)\] x 100% True positives = positive signal from imaging system and cancer found in tissue by pathology False positives = positive signal from imaging system and no cancer found in tissue by pathology True negatives = negative signal from imaging system and no cancer found in tissue by pathology False negatives = negative signal from imaging system and cancer found in tissue by pathology
Time frame: 1 day
Population: Intent to treat population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Phase A No LUM015 | (Phase B Only)Sensitivity and Specificity of the Lumicell Imaging System for Detecting Cancer | Sensitivity | 84 percentage of measurements |
| Phase A No LUM015 | (Phase B Only)Sensitivity and Specificity of the Lumicell Imaging System for Detecting Cancer | Specificity | 73 percentage of measurements |
Secondary
Number of Patients With Adverse Events as a Measure of Safety of the LUM Imaging System in Breast Cancer Subjects.
Serious Adverse Events: Include adverse events that result in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Non-Serious Adverse Events: Adverse events that are not Serious Adverse Events.
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: Intent to treat population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase A No LUM015 | Number of Patients With Adverse Events as a Measure of Safety of the LUM Imaging System in Breast Cancer Subjects. | Serious Adverse Event | 0 Participants |
| Phase A No LUM015 | Number of Patients With Adverse Events as a Measure of Safety of the LUM Imaging System in Breast Cancer Subjects. | Non-Serious Adverse Event | 0 Participants |
| Phase A 0.5 mg/kg | Number of Patients With Adverse Events as a Measure of Safety of the LUM Imaging System in Breast Cancer Subjects. | Non-Serious Adverse Event | 0 Participants |
| Phase A 0.5 mg/kg | Number of Patients With Adverse Events as a Measure of Safety of the LUM Imaging System in Breast Cancer Subjects. | Serious Adverse Event | 0 Participants |
| Phase A 1.0 mg/kg | Number of Patients With Adverse Events as a Measure of Safety of the LUM Imaging System in Breast Cancer Subjects. | Serious Adverse Event | 0 Participants |
| Phase A 1.0 mg/kg | Number of Patients With Adverse Events as a Measure of Safety of the LUM Imaging System in Breast Cancer Subjects. | Non-Serious Adverse Event | 0 Participants |
| Phase B: LUM015 1. mg/kg | Number of Patients With Adverse Events as a Measure of Safety of the LUM Imaging System in Breast Cancer Subjects. | Serious Adverse Event | 0 Participants |
| Phase B: LUM015 1. mg/kg | Number of Patients With Adverse Events as a Measure of Safety of the LUM Imaging System in Breast Cancer Subjects. | Non-Serious Adverse Event | 5 Participants |