Intraoperative Detection of Residual Cancer in Breast Cancer

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.

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.

Eligibility Criteria:
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.

Exclusion criteria:

* Subjects who are treated for bilateral breast cancer resection procedure.
* Subjects who are pregnant at the time of diagnosis of their breast cancer; this exclusion is necessary because the teratogenic properties of LUM015 are unknown. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with LUM015, 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 (hormonal or barrier method of birth control, abstinence) upon entering the study and for 60 days after injection of LUM015. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Breast cancer patients are routinely advised against becoming pregnant during treatment, so this requirement does not differ from standard of care.
* Subjects who have taken an investigational drug within 30 days of enrollment.
* Subjects with prolonged QTc interval defined as greater than 480 ms.
* 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 HTN should be stable within these ranges while under pharmaceutical therapy.
* History of allergic reaction attributed to drugs containing 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, 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 because of the potential for pharmacokinetic interactions with LUM015.
* 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 prior ipsilateral breast cancer surgeries, mastectomies, breast reconstructions or implants.
* Subjects who have undergone a surgical biopsy for any reason in the ipsilateral breast performed less than 2 years prior to enrollment of this study.
* 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 will be evaluated with frozen section.