Investigation of Novel Surgical Imaging for Tumor Excision

Study Overview
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Brief Summary
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This is a multi-center, two-arm randomized, blinded pivotal study to demonstrate the safety and efficacy of the LUM Imaging System (LUM015 imaging agent in conjunction with the LUM Imaging Device and decision software), in identifying residual cancer in the lumpectomy bed of female breast cancer patients undergoing breast surgery in order to assist surgeons in reducing the rates of positive margins. All enrolled subjects will be injected with LUM015 prior to surgery. Surgeons are blinded to whether a participant will be randomized into the device arm until after the standard of care lumpectomy is complete. Participants will then be randomized to receiving the device. Therapeutic (LUM guided) shaves will be removed based on the guidance of the LUM Imaging System. Patients will be followed until their first standard of care post-operative follow-up visit.

Detailed Description
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All subjects will be injected with LUM015. The injection of the study drug will occur 2-6 hours prior to surgery at a dose of 1.0 mg/kg. Surgeons will complete the standard of care lumpectomy. Prior to removing any shaves as part of the standard of care, the surgeon will use the LUM Imaging System to scan and image the cavity where shaves will be obtained. The system will not provide guidance. The intent of the standard of care lumpectomy procedure is to achieve negative margins. Randomization of whether the patient will receive the device will be revealed after the completion of the standard of care lumpectomy. If the patient is randomized to the non-device arm, then the surgeon will complete the surgery per their standard practice. If the patient is randomized to the device arm, the surgeon will use the LUM Imaging Device to scan inside the lumpectomy cavity to indicate areas that may contain residual tumor. If the imaging system identifies that there may be cancer cells remaining in the lumpectomy cavity, the surgeon will remove an additional piece of tissue. This process will be continued until a negative reading from the device is obtained or a maximum of 2 shaves of additional tissue has been removed in each orientation. 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 who have consented to completing Quality of Life Questionnaires will be in the study until the schedule of questionnaires is complete. 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.

Official Title
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Pivotal Study of the LUM Imaging System for Assisting Intraoperative Detection of Residual Cancer in the Tumor Bed of Female Patients With Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Combination Product: Study Device Arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have histologically or cytologically confirmed primary invasive breast cancer, ductal carcinoma in situ (DCIS) or primary invasive breast cancer with a DCIS component. Female, age of 18 years or older. 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 breast cancer, as per the exclusion criteria listed below. Subjects must have organ and marrow function within limits as defined below: Leukocytes > 3,000/microlitre (mcL). Platelets > 75,000/mcL total bilirubin within normal institutional limits Aspartate aminotransferase (AST (SGOT))/alanine transaminase (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. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Exclusion Criteria: Subjects who have been diagnosed with bilateral breast cancer and are undergoing bilateral resection procedure Subjects who are pregnant. Breastfeeding should be discontinued if the mothers is treated with Pegulicianine (LUM015) Subjects who are sexually active and not willing/able to use 2 medically acceptable forms of contraception (hormonal or barrier method of birth control, abstinence) upon entering the study and for 60 days after injection of LUM015. Subjects who have taken an investigational drug within 30 days of enrollment. Subjects who will have administration of methylene blue or any dye for sentinel lymph node mapping on the day of the surgery prior to imaging the lumpectomy cavity with the LUM Imaging Device. Subjects who have not recovered from adverse events due to other pharmaceutical or diagnostic agents. Subjects with uncontrolled hypertension defined as persistent systolic blood pressure > 180 mm Hg, or diastolic blood pressure > 110 mm Hg; those subjects with known hypertension (HTN) should be stable with controlled HTN while under pharmaceutical therapy. History of allergic reaction to polyethylene glycol (PEG). History of allergic reaction to any oral or intravenous contrast agents. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, chronic obstructive pulmonary disease (COPD) or asthma requiring hospitalization within the past 12 months, or psychiatric illness/social situations that would limit compliance with study requirements. HIV-positive individuals on combination antiretroviral therapy are ineligible. Any subject for whom the investigator feels participation is not in the best interest of the subject. Subjects undergoing a second lumpectomy procedure because of positive margins in a previous surgery prior to entering this study Subjects with post-biopsy hematomas greater or equal to 2 cm that are visible on physical exam or detected during pre-operative observations. Subjects with prior ipsilateral breast cancer surgeries, mastectomies, breast reconstructions or implants.s with prior ipsilateral breast cancer surgeries, mastectomies, breast reconstructions or implants Subjects with prior ipsilateral reduction mammoplasties (breast reductions) performed less than 2 years prior to enrollment to this study. Subjects previously treated with systemic therapies to treat the cancer to be removed during this clinical investigation, such as neo-adjuvant chemotherapy or hormonal therapy. Subjects undergoing breast conserving surgery whose resected specimen (main lump, shaves, or any other resected tissue) will be evaluated with frozen section after the LUM-guided removal of shaves.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized to receive the device intervention. All subjects will receive the study drug.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Device Intervention: LUM Imaging System used during surgery<br>The LUM Imaging Device will be used to look inside the lumpectomy cavity to see if the dye indicates any areas that may contain residual tumor. If the imaging identifies that there may be cancer cells remaining in the lumpectomy cavity, the surgeon will remove an additional piece of tissue. This process will be continued until a negative reading from the device is obtained or a maximum of 2 shaves of additional tissue has been removed. Patients in this arm will receive the study drug, LUM015. | Combination Product: Study Device Arm<br>* LUM015 will be administered 2 to 6 hours prior to surgery. The LUM Imaging device will be used to assist in the removal of additional tumor tissue.<br>* Other names: LUM Imaging System;|
| No Intervention: Standard of Care Arm<br>The LUM Imaging Device will not be used to guide additional tissue removal. Patients in this arm will receive the study drug, LUM015. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Had Residual Cancer Found in at Least One LUM Imaging System Guided Shave Among All Patients. | Residual cancer was defined as tumor found by pathology in a therapeutic shave after the SOC surgical procedure was completed; that is, tumor that current Standard of Care (SOC) surgery failed to remove. LUM Imaging System was used during the surgery, but the assessment of the outcomes was unknown until the pathology report was available. | Day 1, during surgery | 
| Sensitivity of LUM Imaging System on Cancer in the Lumpectomy Cavity | Sensitivity of LUM Imaging System on cancer was calculated as percentage of tissues with cancer that was removed from lumpectomy cavity due to positive detection by LUM Imaging System. The estimates of the instrument diagnostic sensitivity used Generalized Estimating Equations (GEE) approach. This method was used to analyze correlated data which was modeled with generalized linear model having binomial link function and including correlation cluster and matrix information (here within each subject). LUM Imaging System was used during the surgery, but the assessment of the outcomes was unknown until the pathology report was available. | Day 1, during surgery | 
| Specificity of LUM Imaging System Detection on Cancer in the Lumpectomy Cavity | Specificity of LUM Imaging System Detection on Cancer in the Lumpectomy Cavity was measured as percentage of the negative margins without cancer, that were tested negative by LUM Imaging System. The estimate of the instrument diagnostic specificity used Generalized Estimating Equations (GEE) approach with random effects from intraclass correlation within subjects. | Day 1, during surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection and Conversion of Positive Margins. | Detection of positive margins: Percentage of patients with positive margins after standard of care breast-conserving surgery, all had LUM Imaging System signals above the threshold in the cavity as defined by the tumor detection algorithm. Conversion of positive margins: Percentage of patients with positive margins after standard of care breast-conserving surgery resulted in the negative margin after LUM Imaging System was used. The system was used during the surgery, but the assessment of the outcomes was unknown until the pathology report was available. | Day 1, during surgery | 
| Removal of Residual Cancer Guided by the LUM Imaging System in Participants With Negative Margins After Standard-of-Care Surgery | Percentage of participants having residual tumor removed within subpopulation of having negative margins after Standard of Care surgery. The system was used during the surgery, but the assessment of the outcomes was unknown until the pathology report was available. | Day 1, during surgery | 
| Removal of Residual Cancer Guided by the LUM Imaging System in Subjects With Positive Margins After Standard-of-Care Surgery | Percentage of participants having residual tumor removed within subpopulation of having positive margins after Standard of Care surgery. The system was used during the surgery, but the assessment of the outcomes was unknown until the pathology report was available. | Day 1, during surgery | 
| 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. The system was used during the surgery, but the assessment of the outcomes was unknown until the pathology report was available. | Day 1, during surgery | 
| Contribution of Therapeutic Shaves to Total Volume Removed During Lumpectomy. | Median of the percentages of the volumes of Lumicell Imaging System - guided shaves (therapeutic shaves) out of total volume removed during lumpectomy for each participant were measured. The system was used during the surgery, but the assessment of the outcomes was unknown until the pathology report was available. | Day 1, during surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer surgery, lumpectomy