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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help surgeons see breast cancer tumors more clearly during surgery. By using a special MRI technique and a fluorescent dye called pHLIP ICG (pH Low Insertion Peptide-Indocyanine Green), doctors aim to improve the accuracy of finding and removing cancer. This approach may enhance surgical outcomes by highlighting the tumor and nearby cancerous tissues. Individuals diagnosed with early-stage breast cancer (tumor stage Tis, T1, or T2) who have not yet received treatment might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative approach.

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 prior data suggests that this imaging technique is safe for breast cancer surgery?

Research shows that pHLIP ICG, a new glowing substance, is being tested for safety in surgeries. Until now, researchers have conducted studies in labs, not on people. These lab studies found that pHLIP ICG can help surgeons see cancerous tissues more clearly by making tumors stand out. This trial marks the first time pHLIP ICG is being tested in humans.

As a Phase 1/2 trial, the main goal is to assess its safety for people. Early trials like this begin with small doses to check for any side effects. Therefore, safety information is still being gathered. Participants in this study will be closely monitored to ensure their safety as researchers learn more about how people handle this new imaging agent. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for breast cancer that primarily rely on surgery, chemotherapy, and radiation, pHLIP® ICG offers a fresh approach by using fluorescence to assist in cancer detection. This treatment is unique because it combines MRI with Near-Infrared Fluorescent (NIRF) imaging, allowing surgeons to visualize cancerous tissue in real-time during surgery. Researchers are excited about pHLIP® ICG because it targets acidic environments typical of cancer cells, potentially improving the precision of tumor removal and minimizing damage to healthy tissue. This innovative method could lead to more successful surgeries and better outcomes for patients.

What evidence suggests that this trial's techniques could be effective for breast cancer?

Research shows that pHLIP ICG helps surgeons see cancerous tissues more clearly during breast cancer surgery. Studies have found that pHLIP ICG targets acidic areas, often present in tumors, making it easier to spot and remove cancer cells. Early tests on animals showed this imaging agent effectively highlighted tumors and blood flow, improving surgical accuracy. In this trial, all participants will receive pHLIP ICG as part of the MRI and fluorescent imaging process. This marks the first test of pHLIP ICG in humans, but its ability to target cancer cells based on acidity is promising and could lead to better surgical outcomes. ^{1 2 3 6 7}

Who Is on the Research Team?

Clarissa Lin, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7591906/

pHLIP ICG for delineation of tumors and blood flow during ... In this paper, we report a translational study of a new fluorescent agent for use in surgery, pHLIP ICG, where ICG (indocyanine green) is a ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10965573/

Aiming the magic bullet: targeted delivery of imaging and ... pHLIPs can be used for extracellular and intracellular delivery of a variety of imaging and therapeutic payloads.

3. jnm.snmjournals.org jnm.snmjournals.org/content/64/10/1647

Ambient Light Resistant Shortwave Infrared Fluorescence ... We preclinically show that the pH low-insertion peptide conjugated to indocyanine green (pHLIP ICG), currently in clinical trials, is an excellent candidate ...

4. nature.com nature.com/articles/s41598-019-44873-1

Acid specific dark quencher QC1 pHLIP for multi-spectral ... We have developed a non-invasive optoacoustic imaging strategy that targets the acidic environment of breast cancer.

5. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/ph-low-insertion-peptide-indocyanine-green

Clinical Trials Using pH-Low Insertion Peptide-Indocyanine ... Review the clinical trials studying ph-low insertion peptide-indocyanine green on this list and use the filters to refine the results by age and location.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10004179/

Recent Advances in Imaging Agents Anchored with pH (Low ... In this paper, we describe the current applications of pHLIP-anchored imaging agents for tumor diagnosis and treatment in terms of different molecular imaging ...

7. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1355893/full

Aiming the magic bullet: targeted delivery of imaging and ... The family of pH (Low) Insertion Peptides (pHLIP) comprises a tumor-agnostic technology that uses the low pH (or high acidity) at the surfaces of cells ...