Delayed Sentinel Lymph Node Biopsy in Ductal Cancer in Situ

NCT ID: NCT04722692

Last Updated: 2023-08-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-01

Study Completion Date

2027-12-30

Brief Summary

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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.

Detailed Description

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The SentiNot 2.0 protocol aims to elucidate the effectivity and accuracy of the delayed sentinel lymph node dissection concept (dSLND) when upfront SLND is considered unnecessary, such as in the setting of a preoperative diagnosis of DCIS, in cases of unclear BIRADS 4 or 5 lesions that are planned for diagnostic excisional biopsy or in selected cases of risk reducing mastectomy. Acknowledging the large variance of practice in this setting, the study aims to address pragmatism to allow for inclusion. For this reason, the trial is designed separately and independently for mastectomy and breast conserving surgery, so that participating sites can recruit as fitting in their practice.

In patients included in the SentiNot 2.0 trial, SPIO (MagTrace,2.0 ml) is injected up to 24 hours preoperatively or perioperatively during primary breast surgery on patients with a preoperative diagnosis of DCIS (or suspicious lesions with no clear diagnosis of invasive cancer but, considered for SLND). The SPIO is injected close to the lesion. If injected less than 24 hours before the operation, a 5 minute massage should be performed. Planned breast surgery is performed. The transcutaneous magnetic counts by SentiMag in the axilla is measured at the end of the breast procedure, so as to allow for confirmation that SLND may be identified. Thus,the SLN is consequently marked with SPIO, but not excised.

In this manner, women that have pure DCIS on final histopathological examination have avoided unnecessary upfront SLND.

If there is underlying invasive breast cancer on final histopathological examination, SLND will be performed at a second operation (d-SLND). A preoperative injection of radioisotope (RI) RI will be added to maximize the chance to detect the SLN. SLND will start with a registration of the magnetic and isotope signal in the axilla, and the incision will be placed in relation to the signal. In patients that have undergone mastectomy, tracers are to be injected intracutaneously in the lateral part of the mastectomy scar. The routine use of blue dye (BD) is strongly advised, but is not compulsory. However, if no transcutaneous signal for SPIO and RI is measured in the axilla pre-incision, an injection of BD according local routines will be administered. Subsequently, SLND will be performed. Patients with upgrade to invasive cancer will undergo SLND, but will be randomized with an allocation ratio of 1:1 to SentiMag first or Radioactive probe first. This will mandate the "principal modality" to perform SLND. Every step of the procedure will be controlled; if the principal modality fails, then the surgeon will use the "secondary". If the principal modality succeeds, the secondary will be registered and documented.

The procedure will be divided to the following steps:

* Transcutaneous axillary signal detection
* Subcutaneous axillary detection, after the incision has been performed.
* In situ SLN identification.
* SLN retrieval ex vivo.
* Residual axillary signal ("Background counts"). If a SLND is successfully completed with the primary modality and no residual axillary signal is detected, before completing the procedure, the secondary modality will be undertaken to allow for the detection of "discordance".

Principle modalities maybe either RI or SPIO. If BD is used, dyed lymphatics should be ignored until failure with both modalities has been reached. The success of each modality, principal and secondary, will be controlled per step. If the surgeon documents principle modality failure for a given step, this is to be documented. The intention-to-treat principle will apply, but if there is failure of the modality randomized as principle, then the per-protocol-analysis principle will apply. All SLNs (magnetic, brown, radioactive, blue) will be removed. Palpable nodes may be removed according to surgeon discretion, but should be reported as such. Total technique failure has to be discussed with the patient in advance, and a plan with patient consent consisting of no-surgery, sampling, axillary dissection or treatment according to intraoperative decision has to be available. If no SLN is found, the procedure performed (axillary clearance, sampling. etc) should be discussed in advance with the patient. The SLN may be sent for frozen section in order to avoid a third operation, if SLN metastases are present.

Standard of care patients (SLND performed upfront for diagnoses included in the inclusion criteria or patients going to l-SLND without SPIO) may also be enrolled in the study prospectively as a control arm.Additionally, patient preference will be tolerated and results will be reported for study secondary and other pre-specified endpoints. Patients in the control group has to be informed that their un-identified data will be used as a comparison and, an oral consent has to be given before surgery regardless whether SLND is planned or not. This will allow for controlled real world data from a prospective control arm in fashion of a cohort.

Conditions

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DCIS Breast Cancer Breast Neoplasms Sentinel Lymph Node

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Delayed SLND (SPIO-first arm)

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 Type EXPERIMENTAL

Delayed SLND

Intervention Type 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.

Late SLND (RI-first arm)

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.

Group Type ACTIVE_COMPARATOR

Late SLND

Intervention Type 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.

Interventions

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Delayed SLND

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.

Intervention Type DIAGNOSTIC_TEST

Late SLND

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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

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).

Exclusion Criteria

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

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Västmanlands Hospital, Västerås, Sweden

UNKNOWN

Sponsor Role collaborator

Sahlgrenska University Hospital

OTHER

Sponsor Role collaborator

University Hospital, Linkoeping

OTHER

Sponsor Role collaborator

Skane University Hospital

OTHER

Sponsor Role collaborator

Blekinge County Council Hospital

OTHER

Sponsor Role collaborator

Växjö Hospital, Växjö, Sweden

UNKNOWN

Sponsor Role collaborator

The University of Hong Kong-Shenzhen Hospital

OTHER

Sponsor Role collaborator

Norrlands University Hospital

OTHER

Sponsor Role collaborator

Dalarna County Hospital, Falun, Sweden

UNKNOWN

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

Uppsala University

OTHER

Sponsor Role lead

Responsible Party

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Andreas Karakatsanis

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Andreas Karakatsanis, PhD

Role: PRINCIPAL_INVESTIGATOR

Uppsala University

Locations

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Baylor College Of Medicine

Houston, Texas, United States

Site Status RECRUITING

The University of Hong Kong-Shenzhen Hospital

Hong Kong, , Hong Kong

Site Status RECRUITING

Falun Lasarett

Falun, Dalarna County, Sweden

Site Status RECRUITING

Växjö County Hospital

Vaxjo, Kronoberg County, Sweden

Site Status RECRUITING

Skåne University Hospital

Lund, Skåne County, Sweden

Site Status RECRUITING

Västmanland County Hospital

Västerås, Västmanland County, Sweden

Site Status RECRUITING

Sahlgrenska University Hospital

Gothenburg, Västra Götaland County, Sweden

Site Status RECRUITING

Uppsala University Hospital

Uppsala, , Sweden

Site Status RECRUITING

Linköping University Hospital

Linköping, Östra Götaland, Sweden

Site Status RECRUITING

Countries

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United States Hong Kong Sweden

Central Contacts

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Andreas Karakatsanis, PhD

Role: CONTACT

+46765864826

Fredrik Wärnberg, PhD

Role: CONTACT

Facility Contacts

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Alastair Thompson

Role: primary

Ava Kwong

Role: primary

Gunilla Christenson

Role: primary

Imad Mohamed

Role: primary

Emma Nimeus

Role: primary

Staffan Eriksson

Role: primary

Fredrik Wärnberg

Role: primary

Andreas Karakatsanis

Role: primary

+46765864826

Guyla Nagy, MD

Role: primary

Eva Vikhe Patil

Role: backup

Other Identifiers

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UUBreast01

Identifier Type: -

Identifier Source: org_study_id

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