Delayed SLND Tracing for Breast Cancer

(SENTINOT_2 Trial)

Recruiting at 8 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

Trial Summary

What is the purpose of this trial?

The trial aims to investigate the use of superparamagnetic iron oxide (SPIO) nanoparticles as a tracer for delayed sentinel lymph node dissection (d-SLND) in patients where upfront axillary surgery (SLND) is oncologically deemed unnecessary and should be avoided. This includes but is not limited to patients with a preoperative diagnosis of ductal cancer in situ of the breast (DCIS), an unclear BIRADS 4-5 planned for diagnostic excision or women planned for risk reducing mastectomy. SPIO is injected in the primary operation, and should final specimen pathology demonstrate invasive breast cancer, only then is an operation in the axilla (d-SLND) performed.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment Delayed Sentinel Lymph Node Biopsy, Delayed Sentinel Lymph Node Dissection, d-SLND, Superparamagnetic Iron Oxide (SPIO) Guided Sentinel Lymph Node Biopsy for breast cancer?

Research shows that using superparamagnetic iron oxide (SPIO) for sentinel lymph node biopsy in breast cancer is as effective as the traditional method using radioisotopes. Studies have found SPIO to be a safe and feasible alternative, with successful detection of sentinel nodes in all patients tested. ^{1 2 3 4 5}

Is Delayed SLND Tracing for Breast Cancer safe for humans?

Studies using superparamagnetic iron oxide (SPIO) for sentinel lymph node biopsy in breast cancer patients have shown it to be safe, with no serious adverse events reported. ^{1 2 3 6 7}

How does the Delayed SLND Tracing treatment for breast cancer differ from other treatments?

The Delayed SLND Tracing treatment for breast cancer uses superparamagnetic iron oxide (SPIO) nanoparticles as a tracer instead of the traditional radioisotopes and blue dye. This method is unique because it avoids radiation exposure and logistical challenges associated with radioisotopes, offering a non-invasive and effective alternative for identifying sentinel lymph nodes. ^{1 2 5 6 7}

Research Team

Andreas Karakatsanis, PhD

Principal Investigator

Uppsala University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Superparamagnetic iron oxide nanoparticles as the sole method for sentinel node biopsy detection in patients with breast cancer. [2022]

2. England 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. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Superparamagnetic Iron Oxide for Identifying Sentinel Lymph Node in Breast Cancer after Neoadjuvant Chemotherapy: Feasibility Study. [2021]

4. United States 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. [2023]

5. England 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. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

Magnetic resonance lymphography of sentinel lymph nodes in patients with breast cancer using superparamagnetic iron oxide: a feasibility study. [2016]

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

Sentinel Lymph Node Biopsy in Early Breast Cancer: Magnetic Tracer as the Only Localizing Agent. [2023]