Investigation of Novel Surgical Imaging for Tumor Excision

NCT03686215 | Completed Phase 3 Results DMC FDA Drug FDA Device

• 2 other identifiers: CL00075R44CA211013-02
• Study Type: interventional
• Target: 406
• Locations: 1 country
• Sites: 14

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.

Conditions

Breast Cancer

Keywords

breast cancer surgery; lumpectomy

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Detection and Conversion of Positive Margins.

  Day 1, during surgery

• Removal of Residual Cancer Guided by the LUM Imaging System in Participants With Negative Margins After Standard-of-Care Surgery

  Day 1, during surgery

• Removal of Residual Cancer Guided by the LUM Imaging System in Subjects With Positive Margins After Standard-of-Care Surgery

  Day 1, during surgery

• Volume of Therapeutic Shaves Removed During Lumpectomy.

  Day 1, during surgery

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

  Day 1, during surgery

Study Arms (2)

Device Intervention: LUM Imaging System used during surgery

EXPERIMENTAL

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

Standard of Care Arm

NO INTERVENTION

The LUM Imaging Device will not be used to guide additional tissue removal. Patients in this arm will receive the study drug, LUM015.

Interventions

Study Device Arm COMBINATION_PRODUCT

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.

Also known as: LUM Imaging System

Device Intervention: LUM Imaging System used during surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Lumicell, Inc.: lead
• National Cancer Institute (NCI): collaborator

Study Sites (14)

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, 36604, United States

Location

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

Stanford Hospital and Clinics

Palo Alto, California, 94304, United States

Location

Morton Plant Mease Health Care Oncology Research

Clearwater, Florida, 33756, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Comprehensive Breast Care Center/Beaumont Health

Royal Oak, Michigan, 48073, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Novant Health Salem Surgical Associates

Winston-Salem, North Carolina, 27103, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

CHI Franciscan Research Center

Tacoma, Washington, 98405, United States

Location

Related Publications (1)

• Smith BL, Hunt KK, Carr D, Blumencranz PW, Hwang ES, Gadd MA, Stone K, Dyess DL, Dodge D, Valente S, Dekhne N, Clark P, Lee MC, Samiian L, Lesnikoski BA, Clark L, Smith KP, Chang M, Harris DK, Schlossberg B, Ferrer J, Wapnir IL. Intraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery. NEJM Evid. 2023 Jul;2(7):EVIDoa2200333. doi: 10.1056/EVIDoa2200333. Epub 2023 Apr 27.

  PMID: 38320161 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

Our trial did not take additional margin specimens from cavity orientations with negative Pegulicianine fluorescence-guided (pFGS) readings but scored the pFGS cavity reading as falsely negative if the corresponding lumpectomy margin was positive.

Results Point of Contact

• Title: Jorge Ferrer, PhD
• Organization: Lumicell

jmferrer@lumicell.com

617-571-0592

Study Officials

• Barbara Smith, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Jorge Ferrer, PhD

  Lumicell, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: September 26, 2018
• Study Start: November 4, 2019
• Primary Completion: December 9, 2021
• Study Completion: May 4, 2022
• Last Updated: August 24, 2023
• Results First Posted: August 24, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)