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CompletedNCT03321929Updated May 1, 2023Results posted

Intraoperative Detection of Residual Cancer in Breast Cancer

A Phase 2 interventional study of LUM Imaging System in Breast Cancer, sponsored by Lumicell, Inc.. Completed at 16 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-05-01.

Sponsored by Lumicell, Inc. · Phase 2, Interventional, and Other

Phase
Phase 2
Study type
Interventional
Enrollment
234
Allocation
Not applicable
Ages
18 Years and older
Sex
Female
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Breast Cancer
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
234 participants (actual)

Study arms

  • Experimental
    LUM Imaging System

    Single dose of LUM015 (1.0 mg/kg) will be administered by intravenous injection between 2 to 6 hours prior to surgery. All subjects undergo lumpectomy as standard of care and will have the study intervention, guidance by intraoperative imaging using the LUM Imaging Device

    Combination Product: LUM Imaging System

Interventions

  • Combination productLUM Imaging System

    Drug: LUM015 Device: LUM 2.6 Imaging Device

    Also known as: LUM015

05

What researchers measure

Primary outcomes

  1. Collect Data to Refine and Verify the Tumor Detection Algorithm.

    Data were collected from mITT population, which included all the patients imaged with the LUM Imaging System. This metric measured the residual cancer that current Standard of Care (SOC) lumpectomy failed to remove. It was defined as among all the patients, the percentage of subjects who had residual cancer found in at least one LUM-guided shave (therapeutic shave or "T-shave") after the current initial SOC lumpectomy procedure was completed.

    Time frame: 1 day

Secondary outcomes

  1. Number of Patients With Reported Adverse Events

    Reported adverse events will be assessed and aggregated according to event type, relation to device or drug, and severity.

    Time frame: Patients were evaluated for adverse events from time of injection until standard post-surgery follow-up visit (Median 31 days after lumpectomy).

  2. Tumor Removal Rate in the Whole mITT Population by SOC Margin Status

    Collect data to verify the detection algorithm reported in previous studies by SOC margin status

    Time frame: 1 week

  3. Tumor Removal Rate Within Subjects Having Positive Standard of Care Margins

    Tumor removal rate was measured as the percentage of the subjects who had residual tumor removed guided by Lumicell Imaging System after standard of care (SOC) procedure within subjects who had positive margins after SOC.

    Time frame: 1 Week

  4. Tumor Removal Rate Within Subjects Having All Negative SOC Margins

    Tumor removal rate was measured as the percentage of the subjects who had residual tumor removed guided by Lumicell Imaging System after standard of care (SOC) procedure within subjects who had negative margins after SOC.

    Time frame: 1 Week

  5. Sensitivity and Specificity of the LUM Imaging System in Predicting Residual Cancer in the Cavity

    Sensitivity and specificity were measured at the tissue level for the Lumicell imaging signal for the sensitivity and specificity on the residual tumor in the cavity of corresponding orientations after standard of care (SOC) of Lumpectomy. Generalized Estimating Equation (GEE) has been applied using generalized linear model having binomial link function and compound symmetry working correlation structure within each subject.

    Time frame: 1 Week

  6. Detection and Conversion of Positive Margins in Subjects After BCS SOC

    Conversion was measured as the ratio of the subjects having all the positive margins after BCS SOC converted to negatives after Lumicell Imaging guided procedure. Detection was measured as the ratio of the subjects having all or at least one positive margin after BCS SOC detected by Lumicell Imaging System. BCS: Breast-conserving surgery; SOC: Standard of Care

    Time frame: 1 Week

  7. 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.

    Time frame: 1 Week

  8. Contribution of Therapeutic Shaves to Total Volume Removed During Lumpectomy.

    The contribution of the volumes of Lumicell Imaging System - guided shaves (therapeutic shaves) were measured as percentage of the sum of the volumes of the therapeutic shaves out of the total volume removed during lumpectomy.

    Time frame: 1 Week

Other outcomes

  1. Number of Surgeons Trained on the Use of the LUM Imaging System

    Surgeons were trained on using the LUM Imaging System in preparation for participating in future clinical trials with the LUM Imaging System. Workflows were established at each institution to support the use of the LUM Imaging System and protocol adherence during lumpectomy procedures. Surgeons were not participants in the trial. Surgeons were the Investigators in the trial.

    Time frame: 1 day

06

Results

Posted May 1, 2023
Limitations and caveats
Protocol deviations may have impacted the reported performance. In some patients no LUM shaves were removed either because of protocol deviation or because the protocol limited the number of additional shaves that could be excised at any single margin. These deviations may have precluded full pathologic correlation and evaluation of clinical utility for many of the LUM images and may have prevented conversion of positive margins to negative margins.

Participant flow

Per protocol, the enrolled population are those who were injected with LUM015.

Participant flow — Overall Study
MilestoneLUM Imaging System
Started234
Completed230
Not completed4
Withdrew: Withdrawn prior to lum imaging procedure completed4

Outcome measures

PrimaryCollect Data to Refine and Verify the Tumor Detection Algorithm.

Data were collected from mITT population, which included all the patients imaged with the LUM Imaging System. This metric measured the residual cancer that current Standard of Care (SOC) lumpectomy failed to remove. It was defined as among all the patients, the percentage of subjects who had residual cancer found in at least one LUM-guided shave (therapeutic shave or "T-shave") after the current initial SOC lumpectomy procedure was completed.

Time frame:
1 day
Reported as:
Number · Percentage
Collect Data to Refine and Verify the Tumor Detection Algorithm.
PercentageLUM Imaging System
Collect Data to Refine and Verify the Tumor Detection Algorithm.11.3 (7.5 to 16.1)
SecondaryNumber of Patients With Reported Adverse Events

Reported adverse events will be assessed and aggregated according to event type, relation to device or drug, and severity.

Time frame:
Patients were evaluated for adverse events from time of injection until standard post-surgery follow-up visit (Median 31 days after lumpectomy).
Reported as:
Count of participants · Participants
Number of Patients With Reported Adverse Events
ParticipantsLUM Imaging System
Chromaturia Adverse Events — Mild or Moderate, Not Related0
Chromaturia Adverse Events — Mild or Moderate, Related214
Chromaturia Adverse Events — Severe, Not Related0
Chromaturia Adverse Events — Severe, Related0
Chromaturia Adverse Events — Life Threatening, Not Related0
Chromaturia Adverse Events — Life Threatening, Related0
Non Chromaturia Adverse Events — Mild or Moderate, Not Related33
Non Chromaturia Adverse Events — Mild or Moderate, Related1
Non Chromaturia Adverse Events — Severe, Not Related0
Non Chromaturia Adverse Events — Severe, Related1
Non Chromaturia Adverse Events — Life Threatening, Not Related0
Non Chromaturia Adverse Events — Life Threatening, Related1
SecondaryTumor Removal Rate in the Whole mITT Population by SOC Margin Status

Collect data to verify the detection algorithm reported in previous studies by SOC margin status

Time frame:
1 week
Reported as:
Number · Percentage of All Subjects
Tumor Removal Rate in the Whole mITT Population by SOC Margin Status
Percentage of All SubjectsLUM Imaging System
Percentage of subjects with positive SOC margins having tumor in at least one therapeutic shave.5.2 (2.7 to 8.9)
Percentage of subjects with negative SOC margins having tumor in at least one therapeutic shave.6.1 (3.4 to 10.0)
SecondaryTumor Removal Rate Within Subjects Having Positive Standard of Care Margins

Tumor removal rate was measured as the percentage of the subjects who had residual tumor removed guided by Lumicell Imaging System after standard of care (SOC) procedure within subjects who had positive margins after SOC.

Time frame:
1 Week
Reported as:
Number · Percentage of Subjects
Tumor Removal Rate Within Subjects Having Positive Standard of Care Margins
Percentage of SubjectsLUM Imaging System
Tumor Removal Rate Within Subjects Having Positive Standard of Care Margins31.6 (17.5 to 48.7)
SecondaryTumor Removal Rate Within Subjects Having All Negative SOC Margins

Tumor removal rate was measured as the percentage of the subjects who had residual tumor removed guided by Lumicell Imaging System after standard of care (SOC) procedure within subjects who had negative margins after SOC.

Time frame:
1 Week
Reported as:
Number · Percentage of Subjects
Tumor Removal Rate Within Subjects Having All Negative SOC Margins
Percentage of SubjectsLUM Imaging System
Tumor Removal Rate Within Subjects Having All Negative SOC Margins7.3 (4 to 11.9)
SecondarySensitivity and Specificity of the LUM Imaging System in Predicting Residual Cancer in the Cavity

Sensitivity and specificity were measured at the tissue level for the Lumicell imaging signal for the sensitivity and specificity on the residual tumor in the cavity of corresponding orientations after standard of care (SOC) of Lumpectomy. Generalized Estimating Equation (GEE) has been applied using generalized linear model having binomial link function and compound symmetry working correlation structure within each subject.

Time frame:
1 Week
Reported as:
Number · Percentage
Sensitivity and Specificity of the LUM Imaging System in Predicting Residual Cancer in the Cavity
PercentageLUM Imaging System
Sensitivity (GEE)69.3 (55.8 to 80.1)
Specificity (GEE)71.7 (68.5 to 74.7)
SecondaryDetection and Conversion of Positive Margins in Subjects After BCS SOC

Conversion was measured as the ratio of the subjects having all the positive margins after BCS SOC converted to negatives after Lumicell Imaging guided procedure. Detection was measured as the ratio of the subjects having all or at least one positive margin after BCS SOC detected by Lumicell Imaging System. BCS: Breast-conserving surgery; SOC: Standard of Care

Time frame:
1 Week
Reported as:
Number · Percentage of All Subjects
Detection and Conversion of Positive Margins in Subjects After BCS SOC
Percentage of All SubjectsLUM Imaging System
Percentage of Subjects Having SOC Positive Margins All Converted to Negative15.8 (6 to 31.3)
Percentage of Subjects Having SOC Positive Margins All Detected by Lumicell Device28.9 (15.4 to 45.9)
Percentage of Subjects Having At Least One SOC Positive Margin Detected by Lumicell Device42.1 (26.3 to 59.2)
SecondaryVolume 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.

Time frame:
1 Week
Reported as:
Median · Volume in CM^3
Volume of Therapeutic Shaves Removed During Lumpectomy.
Volume in CM^3LUM Imaging System
Lumpectomy volume (cm3)57.8 (11.5 to 252.7)
SOC shave volume (cm3)6.0 (0.0 to 52.5)
SOC total volume (cm3)65.4 (17.9 to 276.9)
Therapeutic shave volume (cm3)4.0 (0.0 to 102.8)
Total volume (cm3)77.7 (18.8 to 336.8)
Other pre-specifiedNumber of Surgeons Trained on the Use of the LUM Imaging System

Surgeons were trained on using the LUM Imaging System in preparation for participating in future clinical trials with the LUM Imaging System. Workflows were established at each institution to support the use of the LUM Imaging System and protocol adherence during lumpectomy procedures. Surgeons were not participants in the trial. Surgeons were the Investigators in the trial.

Time frame:
1 day
Reported as:
Count of participants · Participants
Number of Surgeons Trained on the Use of the LUM Imaging System
ParticipantsNumber of Surgeons Trained on Using the LUM Imaging System
Number of Surgeons Trained on the Use of the LUM Imaging System38
SecondaryContribution of Therapeutic Shaves to Total Volume Removed During Lumpectomy.

The contribution of the volumes of Lumicell Imaging System - guided shaves (therapeutic shaves) were measured as percentage of the sum of the volumes of the therapeutic shaves out of the total volume removed during lumpectomy.

Time frame:
1 Week
Reported as:
Median · Percentage
Contribution of Therapeutic Shaves to Total Volume Removed During Lumpectomy.
PercentageLUM Imaging System
Contribution of Therapeutic Shaves to Total Volume Removed During Lumpectomy.6.5 (0 to 55.9)

Adverse events

Collected over All adverse events and adverse device effects, both serious and non-serious, and deaths that are encountered from initiation of study intervention, throughout the study, and within the first post-operative follow-up visit should be followed to their resolution, or until the principal investigator assesses them as stable, or the principal investigator determines the event to be irreversible, or the subject is lost to follow-up. Adverse events were assessed up to 30 days after enrollment.. Non-serious events are listed at a .9% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
LUM Imaging System0/234 (0%)1/234 (0.4%)215/234 (91.9%)
Most frequent serious events
Most frequent serious events
EventLUM Imaging System
Anaphylactic ReactionImmune system disorders1/234
Most frequent other events
Most frequent other events
EventLUM Imaging System
ChromaturiaRenal and urinary disorders214/234
SeromaInjury, poisoning and procedural complications5/234
ContusionInjury, poisoning and procedural complications3/234
NauseaGastrointestinal disorders3/234
PruritusSkin and subcutaneous tissue disorders3/234
Alanine aminotransferase increasedInvestigations2/234
HaematomaVascular disorders2/234
Incision site painInjury, poisoning and procedural complications2/234

Baseline characteristics

Age, Continuous
Age, Continuous(years)LUM Imaging System
Mean61.7 ± 9.8
Sex: Female, Male
Sex: Female, Male(Participants)LUM Imaging System
Female234
Male0
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)LUM Imaging System
Hispanic or Latino4
Not Hispanic or Latino220
Unknown or Not Reported10
Race (NIH/OMB)
Race (NIH/OMB)(Participants)LUM Imaging System
American Indian or Alaska Native0
Asian15
Native Hawaiian or Other Pacific Islander0
Black or African American21
White187
More than one race2
Unknown or Not Reported9
Region of Enrollment
Region of Enrollment(participants)LUM Imaging System
United States234
Body Mass Index
Body Mass Index(Kg/m^2)LUM Imaging System
Mean29.0 ± 6.6
Menopausal Status
Menopausal Status(Participants)LUM Imaging System
Post-menopausal187
Pre/Peri-menopausal47
Mammographic breast density
Mammographic breast density(Participants)LUM Imaging System
Almost entirely fatty12
Scattered areas of fibroglandular density119
Heterogeneously dense86
Extremely dense11
Unknown6

1 further baseline measures are reported on the registry.

07

Study locations

16 sites
  • University of South Alabama
    Mobile, Alabama 36604, United States
  • Stanford University Medical Center
    Palo Alto, California 94304, United States
  • Yale University School of Medicine
    New Haven, Connecticut 06511, United States
  • Comprehensive Breast Care Center
    Clearwater, Florida 33756, United States
  • Baptist MD Anderson Cancer Physicians
    Jacksonville, Florida 32207, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Lahey Hospital and Medical Center
    Burlington, Massachusetts 01805, United States
  • Beaumont Royal Oak
    Royal Oak, Michigan 48073, United States
  • Beaumont Troy
    Troy, Michigan 48098, United States
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
  • Novant Health
    Winston-Salem, North Carolina 27103, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • Penn State Hershey Medical Center
    Hershey, Pennsylvania 17033, United States
  • Dallas Breast Center
    Dallas, Texas 75231, United States
  • MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • Franciscan Breast Surgery
    Tacoma, Washington 98405, United States
08

References and documents

Publications

  • Hwang ES, Beitsch P, Blumencranz P, Carr D, Chagpar A, Clark L, Dekhne N, Dodge D, Dyess DL, Gold L, Grobmyer S, Hunt K, Karp S, Lesnikoski BA, Wapnir I, Smith BL; INSITE study team. Clinical Impact of Intraoperative Margin Assessment in Breast-Conserving Surgery With a Novel Pegulicianine Fluorescence-Guided System: A Nonrandomized Controlled Trial. JAMA Surg. 2022 Jul 1;157(7):573-580. doi: 10.1001/jamasurg.2022.1075. PubMed 35544130 ↗

Study documents

  • Study protocol · Feb 15, 2019
  • Statistical analysis plan · May 5, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03321929
Lead sponsor
Lumicell, Inc.
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Oct 26, 2017
Start date
Feb 6, 2018
Primary completion
Apr 10, 2020
Completion
Apr 10, 2020
Results posted
May 1, 2023
Last update
May 1, 2023

Study contacts

Barbara Smith, M.D., Ph.D.
principal investigator · Massachusetts General Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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