Fluorescence Imaging for Breast Cancer Surgery

No longer recruiting at 1 trial location

Overseen By Julie Margenthaler, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Samuel Achilefu

Must not be taking: Investigational agents

Disqualifiers: Lung disease, Pregnant, Breastfeeding, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help surgeons detect all cancer cells during breast cancer surgery using a special fluorescent dye called LS301. The goal is to improve surgical accuracy, reducing the likelihood of leaving cancerous tissue behind. Participants will receive LS301 before surgery, and the surgical team will use advanced goggles to determine if the dye aids in identifying cancer cells. Ideal participants are those newly diagnosed with Stage I-II breast cancer who are scheduled for breast-conserving surgery and a lymph node biopsy. As a Phase 1 trial, this research aims to understand how LS301 works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking any investigational agents, you would not be eligible to participate.

What prior data suggests that this fluorescence imaging technique is safe for breast cancer surgery?

Research shows that LS301, a new imaging agent, is being tested for safety and effectiveness in breast cancer surgeries. The main goal is to enhance surgical precision by making cancer cells glow during operations. In other studies, researchers prioritized safety and examined how well patients tolerated a single dose of LS301.

Patients in these studies generally tolerated LS301 well, and no major safety concerns have been reported. Since this trial is in the early stages, safety data collection is ongoing. However, LS301's progression into later testing stages suggests it hasn't caused serious problems so far.

Overall, the studies have focused on ensuring LS301 is safe for humans. As with any new treatment, some risks might exist, but early results are promising. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about LS301 for breast cancer surgery because it offers a novel way to ensure all cancerous tissue is removed during surgery. Unlike traditional methods, LS301 uses fluorescence imaging, allowing surgeons to see real-time cancer presence with the help of Cancer Vision Goggles. This innovative approach aims to enhance surgical precision, potentially reducing the need for follow-up surgeries and improving patient outcomes.

What evidence suggests that this fluorescence imaging technique is effective for breast cancer surgery?

Research has shown that LS301, a new imaging tool, could help surgeons see breast cancer cells more clearly during surgery. Early animal studies found that LS301 effectively highlights cancer cells, aiding surgeons in more complete tumor removal. This method aims to reduce the risk of leaving cancerous tissues behind. Currently, about 20% of surgeries miss some cancer cells, but using LS301 might lower that rate to under 5%. In this trial, participants will receive different doses of LS301 to evaluate its safety and effectiveness in highlighting cancer cells during surgery. This evidence suggests LS301 could improve surgical outcomes for breast cancer patients. ^{1 2 3 4 5}

Who Is on the Research Team?

Deborah E Farr, MD

Principal Investigator

UT Southwestern Medical Center

Samuel Achilefu, Ph.D.

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed Stage I-II breast cancer, planning to have breast-conserving therapy and SLN biopsy. They must understand and sign consent. Excluded are breastfeeding or pregnant women, those unfit for surgery, on other trials, with lung disease or allergies to study agents like ICG.

Inclusion Criteria

No signs of enlarged lymph nodes during a physical examination.

I have early-stage breast cancer and am getting a lumpectomy and sentinel lymph node biopsy.

Able to understand and willing to sign a written informed consent document

Exclusion Criteria

I cannot have surgery due to health risks.

I am not pregnant and have a recent negative pregnancy test.

Receiving any investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I - Dose Escalation

Determine the safety and optimal imaging dose of LS301 injected in breast cancer patients using a rolling six design.

18 months

Multiple visits for dose administration and monitoring

Phase I - Dose Expansion

Expansion cohort to test the MTD with 9 patients to recommend an optimal imaging dose for Phase II.

Estimated 6 months

Visits for surgery and imaging assessment

Phase II

Assess the diagnostic capabilities of LS301 for identification of positive margins at surgery.

Estimated 12 months

Visits for surgery and imaging assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• LS301

Trial Overview The trial tests Cancer Vision Goggles (CVG) combined with LS301 dye during surgery to see if they can better identify cancer cells and reduce positive margins in breast cancer surgeries. Phase 1 checks safety/dose of LS301; Phase 2 assesses its ability to detect cancer at surgical margins.

How Is the Trial Designed?

Group I: Phase II: LS301 Experimental Treatment 3 Interventions

* Patient will undergo surgery 4-24 hours after administration of LS301 (dose to be determined in Phase I portion) * Excised tissue will be examined for the presence of LS301 fluorescence using the Cancer Vision Goggles (CVG) to determine if LS301 accumulated in the breast cancer. The investigators will quantify fluorescence intensity in the cancer to establish the feasibility of observing LS301 fluorescence with the imaging system. FDA-approved fluorescence imaging systems may be used to benchmark CVG data.

Group II: Phase I Dose Level 3: LS301 Experimental Treatment 3 Interventions

* Patient will undergo surgery 4-24 hours after administration of LS301 (0.1 mg/kg) * Excised tissue will be examined for the presence of LS301 fluorescence using the Cancer Vision Goggles (CVG) to determine if LS301 accumulated in the breast cancer. The investigators will quantify fluorescence intensity in the cancer to establish the feasibility of observing LS301 fluorescence with the imaging system. FDA-approved fluorescence imaging systems may be used to benchmark CVG data.

Group III: Phase I Dose Level 2: LS301 Experimental Treatment 3 Interventions

* Patient will undergo surgery 4-24 hours after administration of LS301 (0.075 mg/kg) * Excised tissue will be examined for the presence of LS301 fluorescence using the Cancer Vision Goggles (CVG) to determine if LS301 accumulated in the breast cancer. The investigators will quantify fluorescence intensity in the cancer to establish the feasibility of observing LS301 fluorescence with the imaging system. FDA-approved fluorescence imaging systems may be used to benchmark CVG data.

Group IV: Phase I Dose Level 1: LS301 Experimental Treatment 3 Interventions

* Patient will undergo surgery 4-24 hours after administration of LS301 (0.05 mg/kg) * Excised tissue will be examined for the presence of LS301 fluorescence using the Cancer Vision Goggles (CVG) to determine if LS301 accumulated in the breast cancer. The investigators will quantify fluorescence intensity in the cancer to establish the feasibility of observing LS301 fluorescence with the imaging system. FDA-approved fluorescence imaging systems may be used to benchmark CVG data.

Group V: Phase I Dose Expansion: LS301 Experimental Treatment 3 Interventions

* Patient will undergo surgery 4-24 hours after administration of LS301 (dose to be determined in Phase I dose escalation portion) * 9 patients will be enrolled (6 invasive ductal carcinoma and 3 DCIS) * Excised tissue will be examined for the presence of LS301 fluorescence using the Cancer Vision Goggles (CVG) to determine if LS301 accumulated in the breast cancer. The investigators will quantify fluorescence intensity in the cancer to establish the feasibility of observing LS301 fluorescence with the imaging system. FDA-approved fluorescence imaging systems may be used to benchmark CVG data.

Who Is Running the Clinical Trial?

Samuel Achilefu

Lead Sponsor

Trials

1

Recruited

100+

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

Fluorescence imaging in surgery provides real-time feedback to surgeons, helping them identify positive tumor margins and make informed decisions about intraoperative treatments, which can improve surgical outcomes.

Significant advancements in optical imaging techniques, such as photoimmunotherapy and multispectral optoacoustic tomography, are being developed to enhance tumor detection and ensure negative surgical margins, potentially leading to better prognosis for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optical innovations in surgery. de Boer, E., Harlaar, NJ., Taruttis, A., et al.[2022]

A novel fluorescence imaging method for identifying sentinel lymph nodes (SLN) in 25 breast cancer patients showed a high detection rate and low false-negative rate, successfully visualizing lymphatic channels and SLNs in all cases.

The technique, which involved injecting indocyanine green and indigo carmine, allowed for real-time observation during surgery and accurately identified all patients with lymph node metastases, demonstrating its feasibility and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative identification of sentinel lymph nodes by near-infrared fluorescence imaging in patients with breast cancer. Tagaya, N., Yamazaki, R., Nakagawa, A., et al.[2015]

A review of dyes used in sentinel lymph node biopsy (SLNB) for breast cancer revealed that while they generally have acceptable identification rates, they can cause side effects ranging from minor to life-threatening.

Different dyes, such as isosulfan blue, patent blue, and methylene blue, exhibit varying safety profiles, indicating a need for further research to better understand their risks and benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Properties and characteristics of the dyes injected to assist axillary sentinel node localization in breast surgery. Masannat, Y., Shenoy, H., Speirs, V., et al.[2015]

The developed optical visible spectral imaging platform demonstrated a high signal to noise ratio (SNR) greater than 100 and less than 15% error in measuring optical properties, indicating its potential effectiveness in distinguishing between negative and close/positive surgical margins during breast conserving surgery.

The system showed a sensing depth of 0.5-2.2 mm, aligning with the pathologic criterion for clear margins, and exhibited reproducibility with a low coefficient of variation, although improvements in imaging speed are needed for practical intra-operative use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance metrics of an optical spectral imaging system for intra-operative assessment of breast tumor margins. Bydlon, TM., Kennedy, SA., Richards, LM., et al.[2021]

The OPAL system, which uses fluorescence imaging, significantly enhances intraoperative surgical guidance by providing real-time, high-resolution mapping of target tissues, improving the accuracy of tumor resections.

In large animal models, the OPAL system successfully highlighted lymph nodes during surgery, demonstrating its potential to improve surgical outcomes by allowing surgeons to visualize tissues that are otherwise invisible to the naked eye.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Dynamic Optical Projection of Acquired Luminescence for Sentinel Lymph Node Biopsy in Large Animals. Ringhausen, E., Wang, T., Pitts, J., et al.[2018]

The fluorescent imaging agent ICG-p28 allows for rapid localization of tumor lesions during breast-conserving surgery, helping surgeons achieve negative margins and reduce tumor recurrence rates.

ICG-p28 demonstrated no significant toxicity in breast cancer and normal cell lines, indicating it is a safe and effective tool for intraoperative imaging in breast cancer surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nontoxic Tumor-Targeting Optical Agents for Intraoperative Breast Tumor Imaging. Naffouje, SA., Goto, M., Coward, LU., et al.[2022]

A new multispectral open-air fluorescence imaging system has been developed that can effectively detect weak fluorescence signals from malignant tissues during surgery, even in bright surgical lighting conditions.

This system enhances surgical decision-making by accurately identifying cancerous tissues, potentially reducing the need for additional surgeries or treatments, as validated by studies on mice and dogs with cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multispectral open-air intraoperative fluorescence imaging. Behrooz, A., Waterman, P., Vasquez, KO., et al.[2018]

The cathepsin-targeted fluorescent probe VGT-309 was developed to improve tumor detection during breast-conserving surgery, showing specific activation by cathepsins and increased tumor-to-background contrast in imaging over time.

Using VGT-309 in image-guided surgery demonstrated its potential to enhance the accuracy of tumor delineation, which could lead to more complete tumor resections and potentially lower reoperation rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorescent image-guided surgery in breast cancer by intravenous application of a quenched fluorescence activity-based probe for cysteine cathepsins in a syngeneic mouse model. Suurs, FV., Qiu, SQ., Yim, JJ., et al.[2020]

In a study involving 61 breast cancer patients, the use of fluorescein and blue LED light for sentinel lymph node (SLN) detection achieved a high visualization rate of 93.4%, demonstrating its effectiveness as an alternative to traditional methods.

The technique was found to be safe, with no complications reported from the use of fluorescein or blue LED light, making it a promising option that reduces radiation exposure associated with conventional agents like technetium-99m.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel lymph node detection using fluorescein and blue light-emitting diodes in patients with breast carcinoma: A single-center prospective study. Chang, YW., Lee, HY., Lee, CM., et al.[2020]

A new fluorescence-based smartphone imaging and spectroscopy device has been developed for real-time detection of invasive ductal carcinoma (IDC) during surgery, showing high accuracy (93%) in classifying cancerous tissues compared to normal ones.

The device demonstrated significant spectral changes, such as a red shift and increased fluorescence intensity in cancerous tissues, indicating its potential for effective tumor margin detection and classification during breast cancer surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Point-of-care devices based on fluorescence imaging and spectroscopy for tumor margin detection during breast cancer surgery: Towards breast conservation treatment. Thapa, P., Singh, V., Gupta, K., et al.[2023]

A study involving 20 breast cancer specimens demonstrated that a classification algorithm using fluorescence lifetime imaging (FLIm) could accurately detect cancerous tissue with over 97% accuracy, which is crucial for evaluating surgical margins.

This technique has the potential to significantly reduce re-excision rates for breast cancer lumpectomy procedures by identifying positive margins during surgery, rather than waiting for traditional histologic analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated detection of breast cancer in resected specimens with fluorescence lifetime imaging. Phipps, JE., Gorpas, D., Unger, J., et al.[2023]

The Artemis handheld NIR fluorescence camera can detect tumor cells as small as 1 mm³ and has a minimum detectable cell count of 2 × 10⁵ cells, making it effective for real-time visualization during cancer surgeries.

In clinical evaluations, the Artemis successfully identified six malignant lesions in patients with liver metastases, demonstrating its potential utility in fluorescence-guided cancer surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and evaluation of the artemis camera for fluorescence-guided cancer surgery. van Driel, PB., van de Giessen, M., Boonstra, MC., et al.[2022]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-06503

LS301-IT in Partial Mastectomy and Sentinel Lymph Node ... The aim of this Phase 1b/2 study is to investigate the safety, efficacy, and pharmacokinetics (PK) of a single dose of LS301-IT, a novel fluorescence imaging ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05900986?cond=%22Carcinoma,%20Ductal,%20Breast%22&aggFilters=status:not%20rec&rank=7

LS301-IT in Partial Mastectomy and Sentinel Lymph Node ... The aim of this Phase 1b/2 study is to investigate the safety, efficacy, and pharmacokinetics (PK) of a single dose of LS301-IT, a novel fluorescence imaging ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20557020

LS301-IT in Partial Mastectomy and Sentinel Lymph Node ... Safety is the primary objective of this study, followed by effectiveness that will be assessed from fluorescence imaging observations and data.

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/415378

LS301-IT in Partial Mastectomy and Sentinel Lymph Node ... The aim of this Phase 1b/2 study is to investigate the safety, efficacy, and pharmacokinetics (PK) of a single dose of LS301-IT, ...

5. trialx.com trialx.com/clinical-trials/listings/236477/real-time-intraoperative-breast-cancer-visualization-for-margin-assessment/

Real-time Intraoperative Breast Cancer Visualization for ... The accurate detection of all cancer cells highlighted by LS301 during surgery will reduce the number of breast cancer patients with margin positivity to less ...