Fluorescence Imaging for Breast Cancer
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: SBI ALApharma Canada, Inc.
Must not be taking: Phototoxic substances
Disqualifiers: Stage 4 cancer, Porphyria, others
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?Breast conserving surgery (BCS) is performed on patients with breast cancer to resect and completely remove the cancer while conserving as much of the surrounding healthy tissue as possible. Current methods do not allow surgeons to determine the completeness of surgical resection in real-time. This often results in the need for a second surgical procedure, or in some cases more than two surgical procedures in order to have confidence that all cancer has been removed.
This Phase 3 study will evaluate the safety and efficacy of the fluorescent imaging agent PD G 506 A for the real-time visualization of cancer during standard of care breast conserving surgery. PD G 506 A is an investigational drug which is converted in the body into a fluorescent molecule that accumulates in cancer cells. Patients receiving PD G 506 A will undergo standard of care breast conserving surgery followed by fluorescence imaging and removal of any potentially cancerous tissue left behind in the surgical cavity.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot use certain phototoxic substances like St. John's wort or certain antibiotics during the perioperative period (around the time of surgery). It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the treatment PD G 506 A for breast cancer?
Research shows that using fluorescence imaging with PD-1 probes can help in accurately identifying and removing breast tumors during surgery, and when combined with PD-1 immunotherapy, it can reduce cancer recurrence and improve survival in mice. This suggests that similar imaging techniques could be effective in breast cancer treatment.
12345Is fluorescence imaging for breast cancer safe for humans?
Research on similar fluorescence imaging techniques, like those using PD-L1 and PD-1 probes, has shown them to be safe in animal models, with specific targeting and minimal non-specific tissue accumulation. These studies suggest that the imaging process is generally safe, but more human-specific data would be needed for a definitive conclusion.
23456How does fluorescence imaging for breast cancer differ from other treatments?
Fluorescence imaging for breast cancer is unique because it uses a special dye that lights up when exposed to certain light, helping doctors see and remove tumors more accurately during surgery. This method is different from traditional treatments as it provides real-time visualization of tumors, potentially improving surgical outcomes and reducing the risk of cancer recurrence.
34578Eligibility Criteria
This trial is for women aged 18 or older with confirmed primary breast cancer, scheduled for lumpectomy. They must have normal organ and bone marrow function and not be pregnant or breastfeeding. Participants should agree to use contraception and cannot have stage 4 cancer, recent investigational drug use, collagen diseases, or need neoadjuvant therapy.Inclusion Criteria
I am scheduled for surgery to remove a breast tumor.
Women of child-bearing potential must agree to use adequate contraception starting the day entering the study
I am a woman aged 18 or older.
+2 more
Exclusion Criteria
I have had surgery on the breast affected by cancer.
My surgery includes a real-time biopsy analysis.
I have recovered from side effects of any trial drugs or tests taken over a month ago.
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Training
Open-label training phase to optimize workflow for fluorescence imaging during breast conserving surgery
2 weeks
Treatment
Participants receive PD G 506 A or placebo followed by standard of care breast conserving surgery with fluorescence imaging
2 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment, including re-operation rates and patient satisfaction
12 months
Participant Groups
The study tests the PD G 506 A fluorescent imaging agent's safety and effectiveness during breast conserving surgery. It aims to help surgeons see cancer in real-time to potentially reduce the need for additional surgeries by highlighting remaining cancerous tissue after initial removal.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: PD G 506 A + Fluorescence-Guided Resection ArmExperimental Treatment2 Interventions
Patients in this arm will receive PD G 506 A orally approximately 3 hrs prior to anesthesia followed by standard of care BCS. Fluorescence imaging will be performed on tissue specimens resected prior to completion of standard of care resection. Fluorescence imaging performed after SoC BCS is complete will guide the resection of additional tissue.
Group II: Standard of Care ArmPlacebo Group1 Intervention
Patients in this arm will receive the placebo orally approximately 3 hrs prior to anesthesia followed by standard of care BCS. Fluorescence imaging will be performed on tissue specimens resected prior to completion of standard of care resection. Fluorescence-guided resection will not be performed in patients in this arm.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Montefiore Medical CenterBronx, NY
Aurora St. Luke's Medical CentreMilwaukee, WI
Orlando Health, Inc.Orlando, FL
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Who Is Running the Clinical Trial?
SBI ALApharma Canada, Inc.Lead Sponsor
References
Photoimmunotherapy of gastric cancer peritoneal carcinomatosis in a mouse model. [2022]Photoimmunotherapy (PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. We performed PIT in a model of disseminated gastric cancer peritoneal carcinomatosis and monitored efficacy with in vivo GFP fluorescence imaging. In vitro and in vivo experiments were conducted with a HER2-expressing, GFP-expressing, gastric cancer cell line (N87-GFP). A conjugate comprised of a photosensitizer, IR-700, conjugated to trastuzumab (tra-IR700), followed by NIR light was used for PIT. In vitro PIT was evaluated by measuring cytotoxicity with dead staining and a decrease in GFP fluorescence. In vivo PIT was evaluated in a disseminated peritoneal carcinomatosis model and a flank xenograft using tumor volume measurements and GFP fluorescence intensity. In vivo anti-tumor effects of PIT were confirmed by significant reductions in tumor volume (at day 15, p
Developing a Bright NIR-II Fluorophore with Fast Renal Excretion and Its Application in Molecular Imaging of Immune Checkpoint PD-L1. [2023]Fluorescence imaging in the second near-infrared (NIR-II) window holds impressive advantages of enhanced penetration depth and improved signal-to-noise ratio. Bright NIR-II fluorophores with renal excretion ability and low tissue accumulation are favorable for in vivo molecular imaging applications as they can render the target-mediated molecular imaging process easily distinguishable. Here, a probe (anti-PD-L1-BGP6) comprising a fluorophore (IR-BGP6) covalently bonded to the programmed cell death ligand-1 monoclonal antibody (PD-L1 mAb) for molecular imaging of immune checkpoint PD-L1 (a targeting site upregulated in various tumors for cancer imaging) in the NIR-II window is reported. Through molecular optimization, the bright NIR-II fluorophore IR-BGP6 with fast renal excretion (≈91% excretion in general through urine within the first 10 h postinjection) is developed. The conjugate anti-PD-L1-BGP6 succeeds in profiling PD-L1 expression and realizes efficient noninvasive molecular imaging in vivo, achieving a tumor to normal tissue (T/NT) signal ratio as high as ≈9.5. Compared with the NIR-II fluorophore with high nonspecific tissue accumulation, IR-BGP6 derived PD-L1 imaging significantly enhances the molecular imaging performance, serving as a strong tool for potentially studying underlying mechanism of immunotherapy. The work provides rationales to design renal-excreted NIR-II fluorophores and illustrate their advantages for in vivo molecular imaging.
In vivo quantification of programmed death-ligand-1 expression heterogeneity in tumors using fluorescence lifetime imaging. [2023]Cancer patient selection for immunotherapy is often based on programmed death-ligand-1 (PD-L1) expression as a biomarker. PD-L1 expression is currently quantified using immunohistochemistry, which can only provide snapshots of PD-L1 expression status in microscopic regions of ex vivo specimens. In vivo imaging using targeted agents can capture dynamic variations of PD-L1 expression in entire tumors within and across multiple subjects. Towards this goal, several PD-L1 targeted molecular imaging probes have been evaluated in murine models and humans. However, clinical translation of these probes has been limited due to a significant non-specific accumulation of the imaging probes and the inability of conventional imaging modalities to provide quantitative readouts that can be compared across multiple subjects. Here we report that in vivo time-domain (TD) fluorescence imaging can provide quantitative estimates of baseline tumor PD-L1 heterogeneity across untreated mice and variations in PD-L1 expression across mice undergoing clinically relevant anti-PD1 treatment. This approach relies on a significantly longer fluorescence lifetime (FLT) of PD-L1 specific anti-PD-L1 antibody tagged to IRDye 800CW (αPDL1-800) compared to nonspecific αPDL1-800. Leveraging this unique FLT contrast, we show that PD-L1 expression can be quantified across mice both in superficial breast tumors using planar FLT imaging, and in deep-seated liver tumors (>5 mm depth) using the asymptotic TD algorithm for fluorescence tomography. Our results suggest that FLT contrast can accelerate the preclinical investigation and clinical translation of novel molecular imaging probes by providing robust quantitative readouts of receptor expression that can be readily compared across subjects.
Improved resection and prolonged overall survival with PD-1-IRDye800CW fluorescence probe-guided surgery and PD-1 adjuvant immunotherapy in 4T1 mouse model. [2018]An intraoperative technique to accurately identify microscopic tumor residuals could decrease the risk of positive surgical margins. Several lines of evidence support the expression and immunotherapeutic effect of PD-1 in breast cancer. Here, we sought to develop a fluorescence-labeled PD-1 probe for in vivo breast tumor imaging and image-guided surgery. The efficacy of PD-1 monoclonal antibody (PD-1 mAb) as adjuvant immunotherapy after surgery was also assessed. PD-1-IRDye800CW was developed and examined for its application in tumor imaging and image-guided tumor resection in an immunocompetent 4T1 mouse tumor model. Fluorescence molecular imaging was performed to monitor probe biodistribution and intraoperative imaging. Bioluminescence imaging was performed to monitor tumor growth and evaluate postsurgical tumor residuals, recurrences, and metastases. The PD-1-IRDye800CW exhibited a specific signal at the tumor region compared with the IgG control. Furthermore, PD-1-IRDye800CW-guided surgery combined with PD-1 adjuvant immunotherapy inhibited tumor regrowth and microtumor metastases and thus improved survival rate. Our study demonstrates the feasibility of using PD-1-IRDye800CW for breast tumor imaging and image-guided tumor resection. Moreover, PD-1 mAb adjuvant immunotherapy reduces cancer recurrences and metastases emanating from tumor residuals.
Near-infrared fluorescence-labeled anti-PD-L1-mAb for tumor imaging in human colorectal cancer xenografted mice. [2021]The expression of programmed death ligand-1 (PD-L1) in tumor has been used as a biomarker to predict the anti-PD-L1 immunotherapy response. To develop a noninvasive imaging technique to monitor the dynamic changes in PD-L1 expression in colorectal cancer (CRC), we labeled an anti-PD-L1 monoclonal antibody with near-infrared (NIR) dye and tested the ability of the NIR-PD-L1-mAb probe to monitor the PD-L1 expression in CRC-xenografted mice by performing optical imaging. Consistent with the expression levels of PD-L1 protein in three CRC cell lines in vitro by flow cytometry and Western blot analyses, our in vivo imaging showed the highest fluorescence signal of the xenografted tumors in mice bearing SW620 CRC cells, followed by tumors derived from SW480 and HCT8 cell lines. We detected the highest fluorescent intensity of the tumor at 120 hours after injection of NIR-PD-L1-mAb. The highest fluorescence intensity was seen in the tumor, followed by the spleen and the liver in SW620 xenografted mice. In SW480 and HCT8 xenografted mice, however, the highest fluorescent signals were detected in the spleen, followed by the liver and the tumor. Our findings indicate that SW620 cells express a higher level of PD-L1, and the NIR-PD-L1-mAb binding to PD-L1 on the surface of CRC cells was specific. The technique was safe and could provide valuable information on PD-L1 expression of the tumor for development of a therapeutic strategy of personized targeted immunotherapies as well as treatment response of patients with CRC.
Novel small 99mTc-labeled affibody molecular probe for PD-L1 receptor imaging. [2022]Label="Objective" NlmCategory="UNASSIGNED">The in vivo imaging of programmed death ligand 1 (PD-L1) can monitor changes in PD-L1 expression and guide programmed death 1 (PD-1) or PD-L1-targeted immune checkpoint therapy. A 99mTc-labeled affibody molecular probe targeting the PD-L1 receptor was prepared and evaluated its tracing effect in PD-L1-overexpressing colon cancer.
Green fluorescent protein imaging of tumour growth, metastasis, and angiogenesis in mouse models. [2019]We have developed a way of imaging metastases in mice by use of tumour cells expressing green fluorescent protein (GFP) that can be used to examine fresh tissue, both in situ and externally. These mice present many new possibilities for research including real-time studies of tumour progression, metastasis, and drug-response evaluations. We have now also introduced the GFP gene, cloned from bioluminescent organisms, into a series of human and rodent cancer-cell lines in vitro, which stably express GFP after transplantation to rodents with metastatic cancer. Techniques were also developed for transduction of tumours by GFP in vivo. With this fluorescent tool, single cells from tumours and metastases can be imaged. GFP-expressing tumours of the colon, prostate, breast, brain, liver, lymph nodes, lung, pancreas, bone, and other organs have also been visualised externally by use of quantitative transcutaneous whole-body fluorescence imaging. GFP technology has also been used for real-time imaging and quantification of angiogenesis.
Multimode Optical Imaging for Translational Chemotherapy: In Vivo Tumor Detection and Delineation by Targeted Gallium Corroles. [2020]We report the feasibility of tumor detection and delineation in vivo using multimode optical imaging of targeted gallium corrole (HerGa). HerGa is highly effective for targeted HER2+ tumor elimination in vivo, and it emits intense fluorescence. These unique characteristics of HerGa prompted us to investigate the potential of HerGa for tumor detection and delineation, by performing multimode optical imaging ex vivo and in vivo; the imaging modes included fluorescence intensity, spectral (including ratiometric), lifetime, and two-photon excited fluorescence, using our custom-built imaging system. While fluorescence intensity imaging provided information about tumor targeting capacity and tumor retention of HerGa, ratiometric spectral imaging offered more quantitative and specific information about HerGa location and accumulation. Most importantly, the fluorescence lifetime imaging of HerGa allowed us to discriminate between tumor and non-tumor regions by fluorescence lifetime differences. Finally, two-photon excited fluorescence images provided highly resolved and thus topologically detailed information around the tumor regions where HerGa accumulates. Taken together, the results shown in this report suggest the feasibility of tumor detection and delineation by multimode optical imaging of HerGa, and fluorescent chemotherapy agents in general. Specifically, the multimode optical imaging can offer complementary and even synergetic information simultaneously in the tumor detection and delineation by HerGa, thus enhancing contrast.