Fluorescence Imaging for Breast Cancer Surgery

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

97 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators' preclinical data have demonstrated the feasibility of fluorescence-guided tumor resection by Cancer Vision Goggles (CVG) with LS301 in animal models. In this study, the investigators will conduct intraoperative imaging procedures that have minimal interference with ongoing surgery. The underlying hypothesis is that 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 than 5%, compared to the current surgical paradigm of greater than 20%. The pilot study will obtain critical data required to address the larger question of surgical margin assessment in a full Phase I clinical trial. Phase 1: to determine the safety and optimal imaging dose of LS301 injected in breast cancer patients. Phase 2: to determine the ability of this novel fluorescence imaging agent to predict the presence of positive margins around partial mastectomy specimens and positive SLNs during surgical therapy for breast cancer.

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 data supports the effectiveness of the treatment LS301, LS301-IT for breast cancer surgery?

Fluorescence imaging, similar to the treatment LS301, LS301-IT, has been shown to help surgeons identify tumor margins during surgery, which can reduce the need for repeat surgeries and improve outcomes. Studies have demonstrated that using fluorescence imaging agents can significantly reduce tumor recurrence rates by providing real-time guidance to achieve negative margins. ^{1 2 3 4 5}

Is fluorescence imaging for breast cancer surgery safe for humans?

Research on similar fluorescent imaging agents, like ICG-p28, shows no significant toxicity in preclinical studies, suggesting they are generally safe for use in humans. ^{4 6 7 8 9}

How does the treatment LS301-IT differ from other breast cancer treatments?

LS301-IT is unique because it uses fluorescence imaging to help surgeons see the exact edges of a breast tumor during surgery, which can reduce the chance of leaving cancerous tissue behind and lower the need for additional surgeries. ^{3 4 10 11 12}

Research Team

Deborah E Farr, MD

Principal Investigator

UT Southwestern Medical Center

Samuel Achilefu, Ph.D.

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Optical innovations in surgery. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Performance metrics of an optical spectral imaging system for intra-operative assessment of breast tumor margins. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Dynamic Optical Projection of Acquired Luminescence for Sentinel Lymph Node Biopsy in Large Animals. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Nontoxic Tumor-Targeting Optical Agents for Intraoperative Breast Tumor Imaging. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Characterization and evaluation of the artemis camera for fluorescence-guided cancer surgery. [2022]

6. Netherlands 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. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Intraoperative identification of sentinel lymph nodes by near-infrared fluorescence imaging in patients with breast cancer. [2015]

8. Germany 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. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Properties and characteristics of the dyes injected to assist axillary sentinel node localization in breast surgery. [2015]

10. United States pubmed.ncbi.nlm.nih.gov

Multispectral open-air intraoperative fluorescence imaging. [2018]

11. United States 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. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Automated detection of breast cancer in resected specimens with fluorescence lifetime imaging. [2023]