Clinical trial NCT03686215: Investigation of Novel Surgical Imaging for Tumor Excision
Official title: Pivotal Study of the LUM Imaging System for Assisting Intraoperative Detection of Residual Cancer in the Tumor Bed of Female Patients With Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: breast cancer surgery
lumpectomy
Lead sponsor: Lumicell, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2018-09-26
Enrollment: 406
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized to receive the device intervention. All subjects will receive the study drug.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Patients Who Had Residual Cancer Found in at Least One LUM Imaging System Guided Shave Among All Patients.
timeFrame: Day 1, during surgery
measure: Sensitivity of LUM Imaging System on Cancer in the Lumpectomy Cavity
timeFrame: Day 1, during surgery
measure: Specificity of LUM Imaging System Detection on Cancer in the Lumpectomy Cavity
timeFrame: Day 1, during surgery
Secondary outcomes:
measure: Detection and Conversion of Positive Margins.
timeFrame: Day 1, during surgery
measure: Removal of Residual Cancer Guided by the LUM Imaging System in Participants With Negative Margins After Standard-of-Care Surgery
timeFrame: Day 1, during surgery
measure: Removal of Residual Cancer Guided by the LUM Imaging System in Subjects With Positive Margins After Standard-of-Care Surgery
timeFrame: Day 1, during surgery
measure: Volume of Therapeutic Shaves Removed During Lumpectomy.
timeFrame: Day 1, during surgery
measure: Contribution of Therapeutic Shaves to Total Volume Removed During Lumpectomy.
timeFrame: Day 1, during surgery
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama Mitchell Cancer Institute
state: Alabama
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Palo Alto
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Clearwater
country: United States
facility: Morton Plant Mease Health Care Oncology Research
state: Florida
city: Jacksonville
country: United States
facility: Baptist MD Anderson Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Royal Oak
country: United States
facility: Comprehensive Breast Care Center/Beaumont Health
state: Michigan
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Salem Surgical Associates
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Tacoma
country: United States
facility: CHI Franciscan Research Center
state: Washington
Study officials:
affiliation: Massachusetts General Hospital
name: Barbara Smith, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lumicell, Inc.
name: Jorge Ferrer, PhD
role: STUDY_DIRECTOR
References: