Fluorescence Imaging for Breast Cancer Surgery
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Samuel Achilefu
Must not be taking: Investigational agents
Disqualifiers: Lung disease, Pregnant, Breastfeeding, others
No Placebo Group
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.12345
Is fluorescence imaging for breast cancer surgery safe for humans?
How does the treatment LS301-IT differ from other breast cancer treatments?
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 am 18 years old or older.
I have early-stage breast cancer and am getting a lumpectomy and sentinel lymph node biopsy.
See 1 more
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
See 3 more
Trial 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 (Fluorescence Imaging Agent)
Trial OverviewThe 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
5Treatment groups
Experimental Treatment
Group I: Phase II: LS301Experimental Treatment3 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: LS301Experimental Treatment3 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: LS301Experimental Treatment3 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: LS301Experimental Treatment3 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: LS301Experimental Treatment3 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Washington University School of MedicineSaint Louis, MO
UT Southwestern Medical CenterDallas, TX
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Who Is Running the Clinical Trial?
Samuel AchilefuLead Sponsor
Washington University School of MedicineLead Sponsor
References
Optical innovations in surgery. [2022]In the past decade, there has been a major drive towards clinical translation of optical and, in particular, fluorescence imaging in surgery. In surgical oncology, radical surgery is characterized by the absence of positive resection margins, a critical factor in improving prognosis. Fluorescence imaging provides the surgeon with reliable and real-time intraoperative feedback to identify surgical targets, including positive tumour margins. It also may enable decisions on the possibility of intraoperative adjuvant treatment, such as brachytherapy, chemotherapy or emerging targeted photodynamic therapy (photoimmunotherapy).
Performance metrics of an optical spectral imaging system for intra-operative assessment of breast tumor margins. [2021]As many as 20-70% of patients undergoing breast conserving surgery require repeat surgeries due to a close or positive surgical margin diagnosed post-operatively [1]. Currently there are no widely accepted tools for intra-operative margin assessment which is a significant unmet clinical need. Our group has developed a first-generation optical visible spectral imaging platform to image the molecular composition of breast tumor margins and has tested it clinically in 48 patients in a previously published study [2]. The goal of this paper is to report on the performance metrics of the system and compare it to clinical criteria for intra-operative tumor margin assessment. The system was found to have an average signal to noise ratio (SNR) >100 and
Evaluation of Dynamic Optical Projection of Acquired Luminescence for Sentinel Lymph Node Biopsy in Large Animals. [2018]Open surgery requiring cytoreduction still remains the primary treatment course for many cancers. The extent of resection is vital for the outcome of surgery, greatly affecting patients' follow-up treatment including need for revision surgery in the case of positive margins, choice of chemotherapy, and overall survival. Existing imaging modalities such as computed tomography, magnetic resonance imaging, and positron emission tomography are useful in the diagnostic stage and long-term monitoring but do not provide the level of temporal or spatial resolution needed for intraoperative surgical guidance. Surgeons must instead rely on visual evaluation and palpation in order to distinguish tumors from surrounding tissues. Fluorescence imaging provides high-resolution, real-time mapping with the use of a contrast agent and can greatly enhance intraoperative imaging. Here we demonstrate an intraoperative, real-time fluorescence imaging system for direct highlighting of target tissues for surgical guidance, optical projection of acquired luminescence (OPAL). Image alignment, accuracy, and resolution was determined in vitro prior to demonstration of feasibility for operating room use in large animal models of sentinel lymph node biopsy. Fluorescence identification of regional lymph nodes after intradermal injection of indocyanine green was performed in pigs with surgical guidance from the OPAL system. Acquired fluorescence images were processed and rapidly reprojected to highlight indocyanine green within the true surgical field. OPAL produced enhanced visualization for resection of lymph nodes at each anatomical location. Results show the optical projection of acquired luminescence system can successfully use fluorescence image capture and projection to provide aligned image data that is invisible to the human eye in the operating room setting.
Nontoxic Tumor-Targeting Optical Agents for Intraoperative Breast Tumor Imaging. [2022]Precise identification of the tumor margins during breast-conserving surgery (BCS) remains a challenge given the lack of visual discrepancy between malignant and surrounding normal tissues. Therefore, we developed a fluorescent imaging agent, ICG-p28, for intraoperative imaging guidance to better aid surgeons in achieving negative margins in BCS. Here, we determined the pharmacokinetics (PK), biodistribution, and preclinical toxicity of ICG-p28. The PK and biodistribution of ICG-p28 indicated rapid tissue uptake and localization at tumor lesions. There were no dose-related effect and no significant toxicity in any of the breast cancer and normal cell lines tested. Furthermore, ICG-p28 was evaluated in clinically relevant settings with transgenic mice that spontaneously developed invasive mammary tumors. Intraoperative imaging with ICG-p28 showed a significant reduction in the tumor recurrence rate. This simple, nontoxic, and cost-effective method can offer a new approach that enables surgeons to intraoperatively identify tumor margins and potentially improves overall outcomes by reducing recurrence rates.
Characterization and evaluation of the artemis camera for fluorescence-guided cancer surgery. [2022]Near-infrared (NIR) fluorescence imaging can provide the surgeon with real-time visualization of, e.g., tumor margins and lymph nodes. We describe and evaluate the Artemis, a novel, handheld NIR fluorescence camera.
Sentinel lymph node detection using fluorescein and blue light-emitting diodes in patients with breast carcinoma: A single-center prospective study. [2020]Label="BACKGROUND" NlmCategory="BACKGROUND">Sentinel lymph node (SLN) biopsy is an essential procedure for lymph node staging in patients with breast carcinoma. Technetium-99m-labelled nanocolloid (99mTc) is the most accurate and widely used lymphatic mapping agent; however, there are concerns pertaining to the associated exposure to radiation. Studies focusing on new agents are required. We aimed to evaluate the feasibility and safety of SLN detection using fluorescein and blue light-emitting diodes (LEDs) in breast carcinoma patients.
Intraoperative identification of sentinel lymph nodes by near-infrared fluorescence imaging in patients with breast cancer. [2015]We present a novel method for sentinel lymph node (SLN) identification by fluorescence imaging that provides a high detection rate and a low false-negativity rate. Twenty-five breast cancer patients with tumors less than 3 cm in diameter were enrolled. A combination of indocyanine green and indigo carmine was injected subdermally in the areola. Subcutaneous lymphatic channels draining from the areola to the axilla were immediately showed by fluorescence imaging. After incising the axillary skin near the point of disappearance of the fluorescence, the SLN was dissected under fluorescence guidance. In all patients, the lymphatic channels and SLN were successfully visualized. The mean number of fluorescent SLN and blue-dyed SLN were 5.5 and 2.3. Eight patients were found to have lymph node metastases pathologically. All of them were recognized by fluorescence imaging. This method is feasible and safe for intraoperative detection of SLN allowing real-time observation without any need for training.
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]The reoperation rate for breast-conserving surgery is as high as 15-30% due to residual tumor in the surgical cavity after surgery. In vivo tumor-targeted optical molecular imaging may serve as a red-flag technique to improve intraoperative surgical margin assessment and to reduce reoperation rates. Cysteine cathepsins are overexpressed in most solid tumor types, including breast cancer. We developed a cathepsin-targeted, quenched fluorescent activity-based probe, VGT-309, and evaluated whether it could be used for tumor detection and image-guided surgery in syngeneic tumor-bearing mice.
Properties and characteristics of the dyes injected to assist axillary sentinel node localization in breast surgery. [2015]A review of the safety profile of dyes injected to assist in sentinel lymph node biopsy (SLNB) in breast cancer.
Multispectral open-air intraoperative fluorescence imaging. [2018]Intraoperative fluorescence imaging informs decisions regarding surgical margins by detecting and localizing signals from fluorescent reporters, labeling targets such as malignant tissues. This guidance reduces the likelihood of undetected malignant tissue remaining after resection, eliminating the need for additional treatment or surgery. The primary challenges in performing open-air intraoperative fluorescence imaging come from the weak intensity of the fluorescence signal in the presence of strong surgical and ambient illumination, and the auto-fluorescence of non-target components, such as tissue, especially in the visible spectral window (400-650 nm). In this work, a multispectral open-air fluorescence imaging system is presented for translational image-guided intraoperative applications, which overcomes these challenges. The system is capable of imaging weak fluorescence signals with nanomolar sensitivity in the presence of surgical illumination. This is done using synchronized fluorescence excitation and image acquisition with real-time background subtraction. Additionally, the system uses a liquid crystal tunable filter for acquisition of multispectral images that are used to spectrally unmix target fluorescence from non-target auto-fluorescence. Results are validated by preclinical studies on murine models and translational canine oncology models.
Point-of-care devices based on fluorescence imaging and spectroscopy for tumor margin detection during breast cancer surgery: Towards breast conservation treatment. [2023]Fluorescence-based methods are highly specific and sensitive and have potential in breast cancer detection. Simultaneous fluorescence imaging and spectroscopy during intraoperative procedures of breast cancer have great advantages in detection of tumor margin as well as in classification of tumor to healthy tissues. Intra-operative real-time confirmation of breast cancer tumor margin is the aim of surgeons, and therefore, there is an urgent need for such techniques and devices which fulfill the surgeon's priorities.
Automated detection of breast cancer in resected specimens with fluorescence lifetime imaging. [2023]Re-excision rates for breast cancer lumpectomy procedures are currently nearly 25% due to surgeons relying on inaccurate or incomplete methods of evaluating specimen margins. The objective of this study was to determine if cancer could be automatically detected in breast specimens from mastectomy and lumpectomy procedures by a classification algorithm that incorporated parameters derived from fluorescence lifetime imaging (FLIm). This study generated a database of co-registered histologic sections and FLIm data from breast cancer specimens (N = 20) and a support vector machine (SVM) classification algorithm able to automatically detect cancerous, fibrous, and adipose breast tissue. Classification accuracies were greater than 97% for automated detection of cancerous, fibrous, and adipose tissue from breast cancer specimens. The classification worked equally well for specimens scanned by hand or with a mechanical stage, demonstrating that the system could be used during surgery or on excised specimens. The ability of this technique to simply discriminate between cancerous and normal breast tissue, in particular to distinguish fibrous breast tissue from tumor, which is notoriously challenging for optical techniques, leads to the conclusion that FLIm has great potential to assess breast cancer margins. Identification of positive margins before waiting for complete histologic analysis could significantly reduce breast cancer re-excision rates.