Fluorescence Imaging for Breast Cancer

Recruiting at 2 trial locations

Overseen By Jagapreetha Visweswaran

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: SBI ALApharma Canada, Inc.

Must not be taking: Phototoxic substances

Disqualifiers: Stage 4 cancer, Porphyria, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

370 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{2 3 4 5 6}

How 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. ^{3 4 5 7 8}

Research Team

Ralph DaCosta, PhD

Principal Investigator

SBI ALApharma Canada

Eligibility 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.

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.

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

Treatment Details

Interventions

• PD G 506 A

Trial Overview 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.

Participant Groups

Group I: PD G 506 A + Fluorescence-Guided Resection Arm Experimental Treatment 2 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 Arm Placebo Group 1 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.

Who Is Running the Clinical Trial?

SBI ALApharma Canada, Inc.

Lead Sponsor

Trials

1

Recruited

370+

Findings from Research

Photoimmunotherapy (PIT) effectively targets and reduces tumor volume in gastric cancer models, showing significant anti-tumor effects with reductions in tumor size and GFP fluorescence intensity after treatment with the trastuzumab-IR700 conjugate and near-infrared light.

The cytotoxic effects of PIT are dependent on the light dose, leading to necrotic cell rupture, which can be monitored by a decrease in GFP fluorescence, making it a useful biomarker for assessing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photoimmunotherapy of gastric cancer peritoneal carcinomatosis in a mouse model. Sato, K., Choyke, PL., Kobayashi, H.[2022]

The newly developed probe anti-PD-L1-BGP6, which uses the bright NIR-II fluorophore IR-BGP6, allows for efficient noninvasive imaging of PD-L1 expression in tumors, achieving a high tumor-to-normal tissue signal ratio of approximately 9.5.

IR-BGP6 demonstrates rapid renal excretion (about 91% within 10 hours), minimizing tissue accumulation and enhancing the clarity of imaging, making it a promising tool for studying cancer immunotherapy mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing a Bright NIR-II Fluorophore with Fast Renal Excretion and Its Application in Molecular Imaging of Immune Checkpoint PD-L1. Wan, H., Ma, H., Zhu, S., et al.[2023]

In vivo time-domain fluorescence imaging can effectively quantify PD-L1 expression in tumors, providing a more dynamic and comprehensive assessment compared to traditional immunohistochemistry methods, which only offer static snapshots.

This imaging technique, utilizing a longer fluorescence lifetime of a PD-L1 specific antibody, allows for accurate measurement of PD-L1 heterogeneity in both superficial and deep tumors, potentially enhancing the selection process for cancer immunotherapy across multiple subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo quantification of programmed death-ligand-1 expression heterogeneity in tumors using fluorescence lifetime imaging. Pal, R., K, M., Matsui, A., et al.[2023]

The PD-1-IRDye800CW probe effectively targets breast tumors for imaging during surgery, allowing for better identification of microscopic tumor residuals, which can help reduce the risk of positive surgical margins.

Combining PD-1-IRDye800CW-guided surgery with PD-1 monoclonal antibody immunotherapy significantly inhibits tumor regrowth and metastases, leading to improved survival rates in a mouse model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved resection and prolonged overall survival with PD-1-IRDye800CW fluorescence probe-guided surgery and PD-1 adjuvant immunotherapy in 4T1 mouse model. Du, Y., Sun, T., Liang, X., et al.[2018]

A new noninvasive imaging technique using a near-infrared (NIR) dye-labeled anti-PD-L1 monoclonal antibody effectively monitors PD-L1 expression in colorectal cancer (CRC) models, showing the highest fluorescence in tumors with high PD-L1 levels.

This imaging method is safe and can help tailor personalized immunotherapy strategies by providing real-time insights into PD-L1 expression in tumors, which is crucial for predicting treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Near-infrared fluorescence-labeled anti-PD-L1-mAb for tumor imaging in human colorectal cancer xenografted mice. Zhang, M., Jiang, H., Zhang, R., et al.[2021]

The 99mTc-PD-L1 affibody molecular probe effectively targets PD-L1-positive tumors, demonstrating a high labeling yield of 95.95% and good stability, making it a promising tool for in vivo imaging of PD-L1 expression in cancer.

This probe shows rapid uptake in PD-L1-positive tumors with minimal retention in PD-L1-negative tumors, indicating its specificity, and it clears quickly from the bloodstream without significant toxic side effects, suggesting a safe profile for potential clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel small 99mTc-labeled affibody molecular probe for PD-L1 receptor imaging. Liang, Z., Hu, X., Hu, H., et al.[2022]

The development of green fluorescent protein (GFP) imaging in mice allows for real-time visualization of tumor progression and metastasis, providing a powerful tool for studying cancer dynamics and drug responses.

This technology enables the imaging of various cancer types, including colon, prostate, and breast cancers, and allows researchers to visualize single cancer cells and assess angiogenesis in vivo, enhancing our understanding of tumor biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Green fluorescent protein imaging of tumour growth, metastasis, and angiogenesis in mouse models. Hoffman, R.[2019]

The study demonstrates that HerGa, a targeted gallium corrole, is effective for both detecting and delineating HER2+ tumors in vivo using advanced multimode optical imaging techniques.

Different imaging modes, particularly fluorescence lifetime imaging, allow for clear differentiation between tumor and non-tumor regions, enhancing the accuracy of tumor localization and potentially improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimode Optical Imaging for Translational Chemotherapy: In Vivo Tumor Detection and Delineation by Targeted Gallium Corroles. Hwang, JY., Gross, Z., Gray, HB., et al.[2020]

References

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

Photoimmunotherapy of gastric cancer peritoneal carcinomatosis in a mouse model. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Developing a Bright NIR-II Fluorophore with Fast Renal Excretion and Its Application in Molecular Imaging of Immune Checkpoint PD-L1. [2023]

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

In vivo quantification of programmed death-ligand-1 expression heterogeneity in tumors using fluorescence lifetime imaging. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Improved resection and prolonged overall survival with PD-1-IRDye800CW fluorescence probe-guided surgery and PD-1 adjuvant immunotherapy in 4T1 mouse model. [2018]

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

Near-infrared fluorescence-labeled anti-PD-L1-mAb for tumor imaging in human colorectal cancer xenografted mice. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Novel small 99mTc-labeled affibody molecular probe for PD-L1 receptor imaging. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Green fluorescent protein imaging of tumour growth, metastasis, and angiogenesis in mouse models. [2019]

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

Multimode Optical Imaging for Translational Chemotherapy: In Vivo Tumor Detection and Delineation by Targeted Gallium Corroles. [2020]