Delayed SLND Tracing for Breast Cancer

(SENTINOT_2 Trial)

Recruiting at 9 trial locations

Overseen By Fredrik Wärnberg, PhD

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Uppsala University

Disqualifiers: Iron intolerance, Iron overload, Pregnant, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to locate and remove lymph nodes in breast cancer patients using tiny iron particles called SPIO (Superparamagnetic Iron Oxide). The goal is to determine if this method, known as Delayed Sentinel Lymph Node Biopsy, is effective for patients who may not need immediate surgery in the armpit area. The trial includes two groups: one uses SPIO as the main signal for surgery, while the other uses a different tracer. It suits those diagnosed with ductal carcinoma in situ (a non-invasive breast cancer) or those undergoing a mastectomy for risk reduction. Participants should not have allergies to iron or conditions like iron overload disease. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using tiny iron particles, known as superparamagnetic iron oxide (SPIO) nanoparticles, to identify important lymph nodes in breast cancer patients is generally safe. Studies have found that patients tolerate SPIO well. In one study, marking lymph nodes with SPIO helped avoid unnecessary treatments and accurately guided further surgery when needed. This approach ensures additional surgery occurs only if invasive cancer is detected, reducing the risk of overtreatment.

No major reports of serious side effects have emerged from using SPIO in these procedures. Patients did not experience significant negative effects related to the tracer, suggesting that SPIO is a safe option for those undergoing this type of cancer surgery. Overall, using SPIO for delayed sentinel lymph node biopsy appears to carry a low risk of complications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Delayed Sentinel Lymph Node Biopsy (SLND) techniques because they explore new ways to improve breast cancer surgery outcomes. Unlike traditional SLND, which often requires immediate node removal during the primary operation, these methods delay the biopsy to a second procedure. This approach allows the use of superparamagnetic iron oxide (SPIO) or technetium (Tc) as the primary tracer for node detection, potentially increasing accuracy. By delaying the procedure, there's also the potential to reduce unnecessary surgeries if invasive cancer isn't detected initially, thereby improving patient experience and outcomes.

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

Studies have shown that tiny iron particles, known as superparamagnetic iron oxide (SPIO) nanoparticles, can help identify lymph nodes that might have cancer in breast cancer patients. This trial compares two approaches: Delayed SLND (SPIO-first arm) and Late SLND (RI-first arm). In the Delayed SLND arm, SPIO serves as the primary detection tracer, enabling doctors to locate these critical lymph nodes without immediate surgery. Research indicates that SPIO effectively marks the sentinel lymph nodes, helping to avoid unnecessary treatments. This approach is particularly beneficial for patients initially diagnosed with ductal carcinoma in situ (DCIS), a non-invasive type of breast cancer. By using SPIO, doctors can decide on further surgery only if invasive cancer is confirmed, reducing the risk of overtreatment. ^{1 2 3 5 6}

Who Is on the Research Team?

Andreas Karakatsanis, PhD

Principal Investigator

Uppsala University

Are You a Good Fit for This Trial?

This trial is for patients with a pre-diagnosis of ductal cancer in situ (DCIS) or suspicious breast lesions, who are undergoing procedures that might affect future sentinel lymph node detection. It's also open to those planning risk-reducing mastectomies or complex oncoplastic surgeries. Excluded are individuals with iron/dextran/SPIO hypersensitivity, iron overload diseases, pregnant/lactating women, and those deprived of liberty or under guardianship.

Inclusion Criteria

I was diagnosed with DCIS and there might be very small invasions.

I am scheduled for a breast surgery due to a suspicious finding but don't have a confirmed cancer diagnosis.

I was diagnosed with a specific type of non-invasive breast condition before surgery.

Exclusion Criteria

Pregnant or lactating patients

I am not under legal supervision or guardianship.

I have a condition that causes too much iron in my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Primary Operation

SPIO is injected up to 24 hours preoperatively or perioperatively during primary breast surgery

1 day

1 visit (in-person)

Delayed Sentinel Lymph Node Dissection (d-SLND)

If invasive cancer is found, reoperation for SLND with the addition of Tc +/- BD is performed

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at 1, 6, and 12 months postoperatively

What Are the Treatments Tested in This Trial?

Interventions

• Delayed Sentinel Lymph Node Biopsy

Trial Overview The study tests the use of superparamagnetic iron oxide nanoparticles as a tracer for delayed sentinel lymph node dissection in breast cancer cases where immediate axillary surgery isn't necessary. If invasive cancer is found after initial surgery, then an operation in the axilla follows.

How Is the Trial Designed?

Group I: Delayed SLND (SPIO-first arm) Experimental Treatment 1 Intervention

All study participants have been injected interstitially with SPIO, 2ml, at the primary operation. Magnetic axillary signal is registered at the end of the procedure but the SLN is not removed. If invasive cancer is found in the specimen, reoperation for SLND with the addition of Tc +/- BD is performed. At reoperation, SPIO is the "primary" detection tracer.

Group II: Late SLND (RI-first arm) Active Control 1 Intervention

All study participants have been injected interstitially with SPIO, 2ml, at the primary operation. Magnetic axillary signal is registered at the end of the procedure but the SLN is not removed. If invasive cancer is found in the specimen, reoperation for SLND with the addition of Tc +/- BD is performed. At reoperation, Tc is the "primary" detection tracer.

Who Is Running the Clinical Trial?

Uppsala University

Lead Sponsor

Trials

529

Recruited

3,333,000+

Sahlgrenska University Hospital

Collaborator

Trials

519

Recruited

387,000+

Vastra Gotaland Region

Collaborator

Trials

689

Recruited

1,455,000+

Skane University Hospital

Collaborator

Trials

177

Recruited

98,800+

Sahlgrenska University Hospital, Sweden

Collaborator

Trials

439

Recruited

307,000+

Norrlands University Hospital

Collaborator

Trials

14

Recruited

9,800+

Dalarna County Hospital, Falun, Sweden

Collaborator

Trials

1

Recruited

500+

Västmanlands Hospital, Västerås, Sweden

Collaborator

Trials

2

Recruited

1,900+

University Hospital, Linkoeping

Collaborator

Trials

192

Recruited

967,000+

Blekinge County Council Hospital

Collaborator

Trials

16

Recruited

11,300+

Published Research Related to This Trial

The MONOS study demonstrated that superparamagnetic iron oxide (SPIO) nanoparticles are a safe and effective alternative to the standard radioisotope 99m Tc for sentinel node biopsy in breast cancer, with comparable detection rates (95.6% for SPIO vs. 96.9% for 99m Tc).

Preoperative injection of SPIO significantly improved tracer-specific detection rates and the number of nodes retrieved compared to perioperative injection, suggesting that this method simplifies logistics and enhances the efficacy of the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superparamagnetic iron oxide nanoparticles as the sole method for sentinel node biopsy detection in patients with breast cancer. Karakatsanis, A., Daskalakis, K., Stålberg, P., et al.[2022]

The study demonstrated that using a superparamagnetic iron oxide (SPIO) tracer for MRI can effectively identify sentinel lymph nodes (SLNs) in breast cancer patients, achieving a success rate of 10 out of 11, comparable to traditional lymphoscintigraphy methods.

SPIO MRI offers a non-invasive, radioisotope-free alternative for pre-operative localization of SLNs, which could enhance patient safety and reduce exposure to radioactive materials during sentinel lymph node biopsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-operative sentinel lymph node localization in breast cancer with superparamagnetic iron oxide MRI: the SentiMAG Multicentre Trial imaging subprotocol. Pouw, JJ., Grootendorst, MR., Bezooijen, R., et al.[2022]

In a study involving 74 female breast cancer patients who received neoadjuvant chemotherapy, superparamagnetic iron oxide (SPIO) was successfully used for sentinel lymph node biopsy, with all patients having detectable sentinel nodes.

The procedure was efficient, with a median lymph node retrieval time of 20 minutes and no serious adverse events reported, indicating that SPIO is a safe and effective alternative for nodal identification in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superparamagnetic Iron Oxide for Identifying Sentinel Lymph Node in Breast Cancer after Neoadjuvant Chemotherapy: Feasibility Study. Kurylcio, A., Pelc, Z., Skórzewska, M., et al.[2021]

In a study of 328 breast cancer patients, superparamagnetic iron oxide (SPIO) was successfully used for sentinel lymph node localization with a high success rate of 98.8%, identifying a total of 1514 sentinel lymph nodes.

SPIO is shown to be a feasible and effective alternative to traditional methods, with the added benefit of fewer disadvantages, making it a promising option for sentinel lymph node mapping in early breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel Lymph Node Biopsy in Early Breast Cancer: Magnetic Tracer as the Only Localizing Agent. Man, V., Wong, TT., Co, M., et al.[2023]

In a study involving 10 patients with breast cancer, the use of superparamagnetic iron oxide (SPIO) for sentinel lymph node (SLN) biopsy successfully identified SLNs in all patients, demonstrating its efficacy as a tracer compared to traditional methods.

The technique showed no severe complications, with only one minor skin reaction noted, indicating a favorable safety profile for using SPIO-MR sentinel lymphography in surgical planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance lymphography of sentinel lymph nodes in patients with breast cancer using superparamagnetic iron oxide: a feasibility study. Shiozawa, M., Kobayashi, S., Sato, Y., et al.[2016]

In a study involving 282 patients with early breast cancer, the superparamagnetic iron oxide (SPIO) technique for sentinel lymph node (SLN) detection was found to be non-inferior to the traditional method using radioisotope and blue dye, with a very high success rate of 99.3%.

The SPIO method not only harvested a higher average number of SLNs (3.3 compared to 2.8) but also demonstrated excellent concordance rates, suggesting it could safely replace the conventional technique for SLN mapping.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Superparamagnetic Iron Oxide (SPIO) Versus Conventional Technique in Sentinel Lymph Node Detection for Breast Cancer: A Randomised Controlled Trial. Man, V., Suen, D., Kwong, A.[2023]

Superparamagnetic iron oxide (SPIO) combined with pre-operative MRI scanning effectively identifies sentinel lymph nodes (SLNs) in melanoma patients, showing promising results in a small study with 6 participants.

The most effective technique involved a 1.0 ml intracutaneous injection of SPIO followed by a two-minute massage, which successfully visualized SLNs in all participants within five minutes, suggesting a simpler and safer alternative to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel lymph node mapping with superparamagnetic iron oxide for melanoma: a pilot study in healthy participants to establish an optimal MRI workflow protocol. Aldenhoven, L., Frotscher, C., Körver-Steeman, R., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10250503/

Delayed Sentinel Lymph Node Dissection in Patients with ... Marking the SLN with SPIO may avoid overtreatment and allow for accurate d-SLND in patients with DCIS.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04722692

NCT04722692 | Delayed Sentinel Lymph Node Biopsy in ... The trial aims to investigate the use of superparamagnetic iron oxide (SPIO) nanoparticles as a tracer for delayed sentinel lymph node dissection (d-SLND) ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S074879832500112X

Use of superparamagnetic iron oxide for sentinel lymph ... The aim of this study was to assess the outcomes of SPIO in breast cancer patients receiving NACT followed by surgery.

4. link.springer.com link.springer.com/article/10.1007/s12672-025-03344-y

The outcome of selective delayed sentinel lymph node ... We aimed to determine the clinical benefits of delaying SLNB (d-SLNB), if upfront axillary staging was omitted in patients with low-risk ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00099

Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer To update the ASCO evidence-based recommendations on the use of sentinel lymph node biopsy (SLNB) in patients with early-stage breast cancer treated with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02249208

Sentinel Lymph Node Biopsy With Superparamagnetic Iron ... The purpose of this study is to determine the detection rate and the false negative rate of sentinel lymph node (SLN) by superparamagnetic iron ...