Investigation of Novel Surgical Imaging for Tumor Excision

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03686215

Acronym

INSITE

Enrollment

406

Registered

2018-09-26

Start date

2019-11-04

Completion date

2022-05-04

Last updated

2023-08-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Keywords

breast cancer surgery, lumpectomy

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.

Interventions

COMBINATION_PRODUCTStudy Device Arm

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Investigator, Outcomes Assessor)

Masking description

Masking will only be applied until the standard of care surgery is complete. At time of randomization, the study arm will be revealed to the study team. The pathologist will be masked to the type of tissue obtained from the patient.

Intervention model description

Subjects will be randomized to receive the device intervention. All subjects will receive the study drug.

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Patients Who Had Residual Cancer Found in at Least One LUM Imaging System Guided Shave Among All Patients.	Day 1, during surgery	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.
Sensitivity of LUM Imaging System on Cancer in the Lumpectomy Cavity	Day 1, during surgery	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.
Specificity of LUM Imaging System Detection on Cancer in the Lumpectomy Cavity	Day 1, during surgery	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.

Secondary

Measure	Time frame	Description
Volume of Therapeutic Shaves Removed During Lumpectomy.	Day 1, during surgery	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.
Detection and Conversion of Positive Margins.	Day 1, during surgery	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.
Contribution of Therapeutic Shaves to Total Volume Removed During Lumpectomy.	Day 1, during surgery	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.
Removal of Residual Cancer Guided by the LUM Imaging System in Participants With Negative Margins After Standard-of-Care Surgery	Day 1, during 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.
Removal of Residual Cancer Guided by the LUM Imaging System in Subjects With Positive Margins After Standard-of-Care Surgery	Day 1, during 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.

Countries

United States

Participant flow

Recruitment details

406 injected with LUM015 (LUMISIGHT), 14 withdrawn before randomization.

Participants by arm

Arm	Count
Device Intervention: LUM Imaging System Used During Surgery The LUM Imaging Device was used to examine inside the lumpectomy cavity to determine if the dye indicated any areas that might contain residual tumor. If the imaging tested positive for the cancer cells remaining in the lumpectomy cavity, the surgeon would remove an additional piece of tissue. This process was continued until a negative reading from the device was obtained or a maximum of 2 shaves of additional tissue had been removed. Patients in this arm received the study drug, LUM015. Study Device Arm: LUM015 was administered 2 to 6 hours prior to surgery. The LUM Imaging device was used to assist in the removal of additional tumor tissue.	357
Standard of Care Arm The LUM Imaging Device was not used to guide additional tissue removal. Patients in this arm received the study drug, LUM015.	35
Withdrawn Before Randomization All the patients injected with LUM015 but withdrawn before randomization.	14
Total	406

Withdrawals & dropouts

Period	Reason	FG000	FG002
Overall Study	Adverse Event	0	7
Overall Study	Device issue	1	2
Overall Study	Physician Decision	0	1
Overall Study	Protocol Violation	0	4

Baseline characteristics

Characteristic	Withdrawn Before Randomization	Total	Standard of Care Arm	Device Intervention: LUM Imaging System Used During Surgery
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	6 Participants	195 Participants	16 Participants	173 Participants
Age, Categorical Between 18 and 65 years	8 Participants	211 Participants	19 Participants	184 Participants
Age, Continuous	61.6 years STANDARD_DEVIATION 11.6	62.3 years STANDARD_DEVIATION 9.7	61.6 years STANDARD_DEVIATION 9.9	62.4 years STANDARD_DEVIATION 9.6
Body Mass Index	29.8 kg/m^2 STANDARD_DEVIATION 6.8	29.9 kg/m^2 STANDARD_DEVIATION 6.6	31.0 kg/m^2 STANDARD_DEVIATION 5.9	29.8 kg/m^2 STANDARD_DEVIATION 6.7
Estrogen Receptor (ER) (+) Genetic Marker from Biopsy ER (-)	1 Participants	25 Participants	5 Participants	19 Participants
Estrogen Receptor (ER) (+) Genetic Marker from Biopsy ER (+)	13 Participants	378 Participants	30 Participants	335 Participants
Estrogen Receptor (ER) (+) Genetic Marker from Biopsy Not available	0 Participants	3 Participants	0 Participants	3 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	12 Participants	1 Participants	11 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants	383 Participants	34 Participants	336 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants	11 Participants	0 Participants	10 Participants
Human Epidermal growth factor Receptor 2 (HER2) (+) Genetic Marker from Biopsy HER2 (-)	13 Participants	319 Participants	26 Participants	280 Participants
Human Epidermal growth factor Receptor 2 (HER2) (+) Genetic Marker from Biopsy HER2 (+)	0 Participants	23 Participants	3 Participants	20 Participants
Human Epidermal growth factor Receptor 2 (HER2) (+) Genetic Marker from Biopsy Unknown	1 Participants	64 Participants	6 Participants	57 Participants
Lymph Nodes Biopsy Lymph Node (-)	2 Participants	60 Participants	7 Participants	51 Participants
Lymph Nodes Biopsy Lymph Node (+)	0 Participants	10 Participants	1 Participants	9 Participants
Lymph Nodes Biopsy No Lymph Node Biopsy	12 Participants	336 Participants	27 Participants	297 Participants
Mammographic breast density Almost Entirely Fatty	0 Participants	5 Participants	0 Participants	5 Participants
Mammographic breast density Extremely Dense	0 Participants	13 Participants	2 Participants	11 Participants
Mammographic breast density Heterogeneously Dense	10 Participants	163 Participants	13 Participants	140 Participants
Mammographic breast density Scattered Areas of Fibroglandular Density	4 Participants	220 Participants	20 Participants	196 Participants
Mammographic breast density Unknown	0 Participants	5 Participants	0 Participants	5 Participants
Menopausal Status Post	12 Participants	339 Participants	28 Participants	299 Participants
Menopausal Status Pre/Peri	2 Participants	67 Participants	7 Participants	58 Participants
Palpability Not palpable Mass	10 Participants	306 Participants	24 Participants	272 Participants
Palpability Palpable Mass	4 Participants	100 Participants	11 Participants	85 Participants
Progesterone Receptor (PR) (+) Genetic Marker from Biopsy PR (-)	1 Participants	54 Participants	5 Participants	48 Participants
Progesterone Receptor (PR) (+) Genetic Marker from Biopsy PR (+)	11 Participants	311 Participants	28 Participants	272 Participants
Progesterone Receptor (PR) (+) Genetic Marker from Biopsy Unknown	2 Participants	41 Participants	2 Participants	37 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	22 Participants	1 Participants	21 Participants
Race (NIH/OMB) Black or African American	0 Participants	26 Participants	4 Participants	22 Participants
Race (NIH/OMB) More than one race	0 Participants	4 Participants	0 Participants	4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	15 Participants	2 Participants	12 Participants
Race (NIH/OMB) White	13 Participants	337 Participants	27 Participants	297 Participants
Region of Enrollment United States	14 participants	406 participants	35 participants	357 participants
Sex: Female, Male Female	14 Participants	406 Participants	35 Participants	357 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants
Triple Negatives Genetic Marker from Biopsy Triple Negatives - No	13 Participants	391 Participants	32 Participants	346 Participants
Triple Negatives Genetic Marker from Biopsy Triple Negatives - Yes	1 Participants	15 Participants	3 Participants	11 Participants
Tumor Histology From Biopsy DCIS only	2 Participants	78 Participants	6 Participants	70 Participants
Tumor Histology From Biopsy IDC +/- DCIS	10 Participants	284 Participants	25 Participants	249 Participants
Tumor Histology From Biopsy IDC + ILC	0 Participants	3 Participants	0 Participants	3 Participants
Tumor Histology From Biopsy ILC +/- DCIS	2 Participants	41 Participants	4 Participants	35 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 357	0 / 35	0 / 14
other Total, other adverse events	334 / 357	32 / 35	13 / 14
serious Total, serious adverse events	3 / 357	0 / 35	2 / 14

Outcome results

Primary

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.