MRI + Fluorescent Imaging for Breast Cancer

Recruiting at 1 trial location

Overseen By Clarissa Lin, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Pregnancy, Liver disease, Claustrophobia, others

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

Compensation: Varies

Number of Visits: 3

55 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out whether pre-operative mpMRI using additional MRI sequences may improve surgical outcomes by providing more accurate information about the extent and acidity of the tumor than standard MRI, and to see whether the use of the fluorescent imaging agent pHLIP ICG and NIRF imaging during surgery is a safe approach that may allow the surgeon to see the tumor and nearby tissues that contain cancer cells more clearly and remove them completely. During the Phase IIa part of this study, the safe dose of pHLIP ICG will be used that makes it easy for the surgeon to see the tumor and the nearby tissues and structures that may contain cancer cells. This study is the first to test pHLIP ICG in people, and the first to test the use of pHLIP ICG with mpMRI and NIRF imaging in surgery for breast cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment pHLIP ICG for breast cancer?

Research shows that pHLIP ICG, a fluorescent imaging agent, effectively highlights tumors for surgical removal by targeting them and marking blood flow, which helps in better tumor delineation and resection. It has been tested in various animal models and has shown promising results in accurately identifying cancerous tissues, suggesting its potential usefulness in breast cancer treatment. ^{1 2 3 4 5}

Is pHLIP ICG safe for use in humans?

Research indicates that pHLIP ICG, a fluorescent imaging agent, is non-toxic in animal studies, including mice and dogs, and effectively marks tumors for surgical removal without harmful effects. ^{1 3 5 6 7}

How does the treatment using MRI and fluorescent imaging for breast cancer differ from other treatments?

This treatment is unique because it combines MRI with shortwave infrared fluorescence imaging (SWIRFI) using a special dye called pHLIP ICG, which helps to clearly identify and mark tumors for surgical removal. This method offers improved contrast and depth sensitivity, allowing for better tumor visualization and resection compared to traditional imaging techniques. ^{1 2 3 5 8}

Research Team

Clarissa Lin, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with a confirmed primary breast cancer diagnosis, who haven't had previous treatments and are planning to have surgery to conserve the breast. The tumor must be stage Tis, T1 or T2 and larger than 1 cm. Participants need to be able to undergo MRI scans without any contraindications.

Inclusion Criteria

My tumor is in an early stage and larger than 1 cm.

I can take care of myself and perform daily activities.

I have not received any previous treatments.

Exclusion Criteria

You weigh over 450 pounds and cannot have an MRI scan.

You can't have a MRI scan because you are very afraid of being in small spaces or feel very anxious during the scan.

You have an implant that is not safe for MRI scans.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative MRI and pHLIP® ICG Administration

Participants undergo pre-operative MRI and receive a single intravenous dose of pHLIP® ICG for intraoperative imaging

1-2 days

1 visit (in-person)

Surgery and Intra-operative Imaging

Participants undergo breast conserving surgery with intra-operative NIRF imaging using pHLIP® ICG

1 day

1 visit (in-person)

Post-surgical Follow-up

Participants return for a routine post-surgical examination and monitoring of adverse events

7-14 days

1 visit (in-person)

Extended Follow-up

Monitoring of serious adverse events and visualization of lesions with pHLIP® ICG

up to 6 months

Treatment Details

Interventions

• pHLIP® ICG

Trial Overview The study tests if pre-operative multiparametric MRI (mpMRI) can improve surgical outcomes by better defining the tumor's extent and acidity compared to standard MRI. It also examines whether pHLIP ICG fluorescent imaging agent used during surgery helps surgeons remove cancer more effectively.

Participant Groups

Group I: MRI and pHLIP® ICG Experimental Treatment 1 Intervention

All study participants in Phase I will receive pre-operative MRI and mpMRI scans, a pre-operative injection of pHLIP ICG, and NIRF imaging during surgery (intra-operatively). During phase IIa of the study, if pHLIP® ICG NIRF imaging indicates tumor in areas outside of the planned resection area, biopsy samples will be taken from these areas and submitted for pathological analysis.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

pHLIP Inc.

Collaborator

Trials

1

Recruited

60+

Stryker Instruments

Industry Sponsor

Trials

17

Recruited

1,500+

Findings from Research

The pH low-insertion peptide conjugated to indocyanine green (pHLIP ICG) demonstrates exceptional sensitivity for cancer-targeted shortwave infrared fluorescence imaging (SWIRFI), achieving picomolar sensitivity (0.4 nM) for tumor detection in a breast cancer mouse model up to 96 hours post-injection.

SWIRFI using pHLIP ICG offers significant advantages, including high signal-to-noise and contrast-to-noise ratios, allowing for effective tumor delineation even in ambient light conditions, which could greatly enhance surgical outcomes in cancer resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ambient Light Resistant Shortwave Infrared Fluorescence Imaging for Preclinical Tumor Delineation via the pH Low-Insertion Peptide Conjugated to Indocyanine Green. Mc Larney, BE., Kim, M., Roberts, S., et al.[2023]

The combination of methylene blue (MB) and the fluorescently labeled pH low insertion peptide (Alexa532-pHLIP) effectively enhances the contrast of pathological breast tissue, allowing for better visualization of cancer cells and tissue morphology.

Alexa532-pHLIP specifically accumulates in cancer cells, while MB stains both cancer and normal cell nuclei, indicating that these two agents provide complementary information that could improve breast cancer detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of dual-contrast fluorescence imaging of pathological breast tissues. Mitrou, A., Feng, X., Khan, A., et al.[2021]

The new fluorescent agent pHLIP ICG is non-toxic and provides prolonged visualization of blood vessels for several hours after intravenous administration, making it useful for image-guided surgery.

pHLIP ICG effectively targets tumors and their surrounding tissue, enhancing the ability to delineate and surgically remove tumors, as demonstrated in various mouse and human tumor models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

pHLIP ICG for delineation of tumors and blood flow during fluorescence-guided surgery. Crawford, T., Moshnikova, A., Roles, S., et al.[2021]

The pH low insertion peptide (pHLIP) conjugated with indocyanine green (ICG) allows for highly accurate visualization of malignant bladder lesions, achieving a sensitivity of 97% and a specificity of 100% in detecting high-grade urothelial carcinomas.

This imaging technique significantly improves early diagnosis of bladder cancer, identifying carcinoma in situ in 11 cases compared to only 4 cases detected using traditional white light methods, suggesting potential for better treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP peptide ex vivo. Golijanin, J., Amin, A., Moshnikova, A., et al.[2018]

The ICG-Var3 pHLIP imaging agent demonstrated 100% sensitivity in identifying malignant upper tract urothelial carcinomas, significantly outperforming conventional white light examination, which had a sensitivity of 78.9%.

This study involved 12 ex-vivo upper urinary tract specimens, and the results suggest that pHLIP-based imaging could enhance the detection and management of upper tract urothelial carcinoma, although further validation in live patients is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex-vivo Imaging of Upper Tract Urothelial Carcinoma Using Novel pH Low Insertion Peptide (Variant 3), a Molecular Imaging Probe. Brito, J., Golijanin, B., Kott, O., et al.[2022]

The pHLIP-FIRE tool effectively images acidic tumors by inserting into cell membranes in these environments, enhancing fluorescence specifically in targeted tissues, which allows for clear visualization of tumor locations.

In studies with mice bearing breast tumors, pHLIP-FIRE demonstrated a strong contrast index of approximately 17, indicating its potential for both direct imaging of tumor cells and targeted delivery of therapeutic cargo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

pHLIP-FIRE, a cell insertion-triggered fluorescent probe for imaging tumors demonstrates targeted cargo delivery in vivo. Karabadzhak, AG., An, M., Yao, L., et al.[2021]

The pHLIP peptide effectively targets acidic tissues, such as tumors and inflammatory sites, with high accuracy, showing a fluorescence signal that is five times stronger in tumors compared to healthy tissue, indicating its potential for early cancer detection.

The mechanism of pHLIP's action relies on its pH-sensitive properties, allowing it to insert into membranes at acidic pH, which is crucial for its accumulation in diseased tissues; modifications to its structure can significantly impair this targeting ability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanism and uses of a membrane peptide that targets tumors and other acidic tissues in vivo. Andreev, OA., Dupuy, AD., Segala, M., et al.[2018]

Indocyanine green (ICG) fluorescence showed prolonged retention in diseased canine mammary tissue for up to 72 hours, indicating its potential as a blood pool agent, but did not differentiate between normal and cancerous tissues based on uptake rates.

In contrast, HPPH-car demonstrated active uptake in malignant tissues due to overexpressed LDL receptors, allowing for differentiation from normal tissue, although its fluorescence was only detectable for 24 hours after administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study. Gurfinkel, M., Thompson, AB., Ralston, W., et al.[2019]

References

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

Ambient Light Resistant Shortwave Infrared Fluorescence Imaging for Preclinical Tumor Delineation via the pH Low-Insertion Peptide Conjugated to Indocyanine Green. [2023]

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

Feasibility of dual-contrast fluorescence imaging of pathological breast tissues. [2021]

3. England pubmed.ncbi.nlm.nih.gov

pHLIP ICG for delineation of tumors and blood flow during fluorescence-guided surgery. [2021]

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

Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP peptide ex vivo. [2018]

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

Ex-vivo Imaging of Upper Tract Urothelial Carcinoma Using Novel pH Low Insertion Peptide (Variant 3), a Molecular Imaging Probe. [2022]

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

pHLIP-FIRE, a cell insertion-triggered fluorescent probe for imaging tumors demonstrates targeted cargo delivery in vivo. [2021]

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

Mechanism and uses of a membrane peptide that targets tumors and other acidic tissues in vivo. [2018]

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

Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue using fluorescence, near-infrared reflectance imaging: a case study. [2019]