Delayed Sentinel Lymph Node Biopsy in Ductal Cancer in Situ

NCT04722692 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: UUBreast01
• Study Type: interventional
• Target: 500
• Locations: 3 countries
• Sites: 9

Brief Summary

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.

Conditions

DCIS; Breast Cancer; Breast Neoplasms; Sentinel Lymph Node

Keywords

Sentinel Lymph Node Dissection; DCIS; Ductal Cancer In situ of the breast; Breast cancer; Superparamagnetic Iron Oxide Nanoparticles; Sentinel Lymph Node; Risk reducing mastectomy

Outcome Measures

Primary Outcomes (3)

• d-SLND detection rate

  Number of subjects in whom SPIO detected at least one node divided by the number of subjects who underwent the SLND procedure. Analyses will be performed cumulatively and +/-BD and per type of surgery (BCT or mastectomy).

  One-time (At operation)

• l-SLND detection rate

  Number of subjects in whom radioisotope detected at least one node divided by the number of subjects who underwent the SLND procedure. Analyses will be performed cumulatively and +/-BD and per type of surgery (BCT or mastectomy).

  One-time (At operation)

• Nodal concordance

  Number of nodes identified by both test (SPIO) and control (isotope) out of all nodes identified. Analyses will be performed cumulatively and +/-BD and per type of surgery (BCT or mastectomy).

  One-time (At operation)

Secondary Outcomes (4)

• SLND avoidance rate

  One-time (At operation)

• Per patient concordance

  One-time (At operation)

• Malignancy rate

  One-time (At operation)

• Nodal Malignancy rate

  One-time (At operation)

Other Outcomes (7)

• Shoulder Arm Morbidity

  Baseline and 1,6,12,24 months postoperatively

• Cost effectiveness

  Baseline, and at 1, 6 and 12 months postoperatively

• Quality-Adjusted-Life-Years (QALY)

  Baseline, and at 1, 6 and 12 months postoperatively

Study Arms (2)

Delayed SLND (SPIO-first arm)

EXPERIMENTAL

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.

Diagnostic Test: Delayed SLND

Late SLND (RI-first arm)

ACTIVE COMPARATOR

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.

Diagnostic Test: Late SLND

Interventions

Delayed SLND DIAGNOSTIC_TEST

SLND performed after surgery for DCIS or other pre-invasive lesions, where final pathology showed invasive breast cancer. Patients have received SPIO in the breast at the first operation, prior to dissection and resection and the SLN has already been marked with SPIO. These SLNs are to be removed. SLND is divided into the following steps: 1. Transcutaneous signal 2. Incision in the axilla (skin, subcutaneous fat and fascia) and "In situ" signal 3. SLN identification "in situ" 4. SLN excision and signal "ex vivo" 5. Background axillary counts. For step "d" the radioactive counts are registered for each SLN that has been excised. When the procedure is completed successfully with SPIO, then background axillary isotope counts are registered and, if present, SLND continues as described above with the isotope as primary tracer.

Delayed SLND (SPIO-first arm)

Late SLND DIAGNOSTIC_TEST

SLND performed after surgery for DCIS or other pre-invasive lesions, where final pathology showed invasive breast cancer. Patients will be injected with radioisotope in the operated breast before SLND according to standard of care. Any SLNs detected with this intervention are to be removed. SLND is divided into the following steps: 1. Transcutaneous signal 2. Incision in the axilla (skin, subcutaneous fat and fascia) and "In situ" signal 3. SLN identification "in situ" 4. SLN excision and signal "ex vivo" 5. Background axillary counts. For step "d" the magnetic counts are registered for each SLN that has been excised. When the procedure is completed successfully with the isotope, then background axillary iSPIO counts are registered and, if present, SLND continues as described above with the SPIO as primary tracer.

Late SLND (RI-first arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Preoperative diagnosis of DCIS, of any grade and any size if planned for mastectomy.
• B. Planned Risk-reducing mastectomy, if it would be considered for upfront SLND due to institutional practice or in case of an individualised recommendation.
• C. Any case with a preoperative diagnosis of pre-invasive or unclear lesion, that upfront SLND would be otherwise considered, such as, but not limited to:
• Patients with a preoperative diagnosis of DCIS grade 3 any size or, DCIS grade 2 larger than or equal to 20 mm on mammography and planned for breast conserving surgery or
• Patients with a preoperative diagnosis of DCIS on core biopsy with a palpable mass on clinical examination or mass effect on radiology or
• Patients with a preoperative diagnosis of DCIS with suspicion of micro-invasion on core biopsy or
• Patients with a mammographic/ultrasound/MRI finding, suspicious for breast cancer (BIRADS 4 or 5) planned for diagnostic excision with breast conserving surgery, with no definitive diagnosis of invasive cancer or
• Patients with a preoperative diagnosis of DCIS, any grade, any size and planned for a complex oncoplastic procedure or
• Patients with a preoperative diagnosis of DCIS, any grade, any size and planned for a procedure that may compromise detection rate for a future SLND, such as, but not confined to: lesions in the upper outer quadrant or the axillary tail, removal of the nipple areola complex and so on or
• The above mentioned categories with a preoperative diagnosis of pleomorphic Lobular Cancer in Situ (pLCIS), classic Lobular Neoplasia (LN) or Atypical Ductal Hyperplasia (ADH).

You may not qualify if:

• Intolerance/hypersensitivity to iron, dextran compounds or SPIO
• An iron overload disease
• Patient deprived of liberty or under guardianship
• Pregnant or lactating patients

Sponsors & Collaborators

• Uppsala University: lead
• Västmanlands Hospital, Västerås, Sweden: collaborator
• Sahlgrenska University Hospital: collaborator
• University Hospital, Linkoeping: collaborator
• Skane University Hospital: collaborator
• Blekinge County Council Hospital: collaborator
• Växjö Hospital, Växjö, Sweden: collaborator
• The University of Hong Kong-Shenzhen Hospital: collaborator
• Norrlands University Hospital: collaborator
• Dalarna County Hospital, Falun, Sweden: collaborator
• Baylor College of Medicine: collaborator

Study Sites (9)

Baylor College Of Medicine

Houston, Texas, 77030, United States

RECRUITING

The University of Hong Kong-Shenzhen Hospital

Hong Kong, Hong Kong

RECRUITING

Falun Lasarett

Falun, Dalarna County, 791131, Sweden

RECRUITING

Växjö County Hospital

Vaxjo, Kronoberg County, 35434, Sweden

RECRUITING

Skåne University Hospital

Lund, Skåne County, 2242, Sweden

RECRUITING

Västmanland County Hospital

Västerås, Västmanland County, 72335, Sweden

RECRUITING

Sahlgrenska University Hospital

Gothenburg, Västra Götaland County, 41346, Sweden

RECRUITING

Uppsala University Hospital

Uppsala, 75185, Sweden

RECRUITING

Linköping University Hospital

Linköping, Östra Götaland, 58191, Sweden

RECRUITING

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating; Breast Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Andreas Karakatsanis, PhD

  Uppsala University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andreas Karakatsanis, PhD

CONTACT

+46765864826; andreas.karakatsanis@surgsci.uu.se

Fredrik Wärnberg, PhD

CONTACT

fredrik.warnberg@vgregion.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: All patients will have been injected with SPIO during the breast procedure. Those who have invasive breast cancer on final pathology will receive radioisotope and undergo SLND. Patients will be randomly allocated to one of two arms: Experimental arm (SLND will be SPIO-guided and the isotope activity will be controlled as background) and control arm (SLND will be isotope-guided and SPIO activity will be controlled as background).

Study Record Dates

• First Submitted: December 23, 2020
• First Posted: January 25, 2021
• Study Start: March 1, 2020
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: August 3, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1); SE (7); US (1)