Feasibility Study of Intraoperative Imaging in Breast Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Feasibility of the LUM Imaging System for Intraoperative Detection of Residual Cancer in the Tumor Bed of Female Subjects With Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: LUM015
* Device: LUM 2.6 Imaging Device


Participation Criteria
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Eligibility Criteria
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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. Exclusion Criteria: Subjects with a known current condition of substance addiction. Subjects who have taken an investigational drug within 30 days of enrollment. Subjects with prolonged QT interval. Subjects who will have administration of methylene blue or any blue dye used for sentinel node mapping procedures. Subjects who have not recovered from adverse events due to pharmaceutical or diagnostic agents administered more than 4 weeks earlier. Subjects with uncontrolled hypertension defined as persistent systolic blood pressure > 150 mm Hg, or diastolic blood pressure > 95 mm Hg; those subjects with known HTN should be stable within these ranges while under pharmaceutical therapy Subjects with insulin dependent diabetes mellitus. History of anaphylactic reaction attributed to any contrast agent or drugs containing polyethylene glycol (PEG). Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, COPD or asthma requiring hospitalization within the past 12 months, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant women are excluded. Breastfeeding should be discontinued if the mother is treated with LUM015. Subjects who are sexually active and not willing/able to use medically acceptable forms of contraception upon entering the study. HIV-positive individuals on combination antiretroviral therapy. Any subject for whom the investigator feels participation is not in the best interest of the subject. Subjects undergoing a second surgery because they had positive margins in a previous surgery. Subjects with prior breast surgeries, mastectomies, breast reconstructions or implants. (Note: subjects who have had prior breast biopsies are not excluded) Subjects with prior reduction mammoplasties or breast reductions performed less than 2 years prior to enrollment to this study. Subjects previously treated with systemic therapies to treat cancer, such as neo-adjuvant chemotherapy or hormonal therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LUM Imaging System<br>No dose or a single dose of LUM015 (0.5 mg/kg or 1.0 mg/kg) will be administered by intravenous injection between 2 to 6 hours prior to surgery. The dose administered in Phase B will be determined based on results of Phase A. All subjects will have intraoperative imaging using the LUM 2.6 Imaging Device. | Drug: LUM015<br> <br> Device: LUM 2.6 Imaging Device<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (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 | 1 day | 
| (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 | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Patients were evaluated for adverse events from time of injection until standard post-surgery follow-up visit. (Median 31 days after lumpectomy). |