Breast CancerNCT05288686
Use of Superparamagnetic Iron Oxide (SPIO) in Sentinel Lymph Node Detection for Breast Cancer
A study testing sentinel lymph node biopsy procedure in people with Breast Cancer and Sentinel Lymph Node, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
Sentinel lymph node biopsy is mandatory during breast cancer operation for disease staging and treatment. The localization of sentinel lymph node is by the injection of radioisotope and blue dye, which is the gold standard. However the use of radioisotope and blue dye are associated with specific drawbacks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Sentinel Lymph Node
- What is being tested?
- sentinel lymph node biopsy procedure
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 282 participants
- Where
- 1 siteHong Kong
- Study dates
- 24 Jul 2018to 30 Jun 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients with clinical T1-3N0 invasive ductal carcinoma or invasive lobular carcinoma planned for breast conservative surgery or mastectomy, with sentinel lymph node biopsy
- Patients planned for upfront operation or neoadjuvant chemotherapy are allowed
Who cannot join
- Patients with hypersensitivity to dextran compounds, iron or blue dye
- Patients with iron overload disease
- Pregnant or lactating patients
- Patients with pacemaker or other implantable metallic devices in chest wall or prosthesis in shoulder
- Mentally incompetent patients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Use of Superparamagnetic Iron Oxide (SPIO) Versus Conventional Radioisotope and Patent Blue Dye in Sentinel Lymph Node Detection for Breast Cancer: a Randomized Controlled Trial
Sentinel lymph node biopsy is mandatory during breast cancer operation for disease staging and treatment. The localization of sentinel lymph node is by the injection of radioisotope and blue dye, which is the gold standard. However the use of radioisotope and blue dye are associated with specific drawbacks. Superparamagnetic iron oxide is a magnetic tracer which is FDA-approved for sentinel lymph node localization. The hypothesis of this study is superparamagnetic iron oxide can replace the conventional dual mapping of radioisotope and blue dye in the detection of sentinel lymph nodes for early breast cancers.
Read the detailed description
Sentinel lymph node biopsy has replaced axillary dissection as the standard of care in clinically node negative breast cancer. Lymphatic mapping with radioisotope and blue dye were most studied tracer agents and their combination was shown to give the highest nodal identification rate and lowest false negative rate. However the use of radioisotope is strictly monitored due to its radioactivity and blue dye is associated with potential allergic reactions and skin tattoo. Superparamagnetic iron oxide is non-radioactive. It gives an audible signal with the magnetometer and a brown color as visual cue. It has demonstrated comparable nodal identification rate with the conventional method in multiple non-inferiority trials in Europe and the USA. There was no randomized controlled trial for a head-to-head comparison between these mapping technique. The hypothesis of this study is superparamagnetic iron oxide alone can replace the conventional dual mapping of radioisotope and blue dye.
Previous literature suggested the nodal detection rate for conventional method and SPIO was around 97%. Assuming a non-inferiorly limit of 5%, with a power of 80% and 5% significance level, the number of patients per treatment arm should be 144. We will need a sample size of 300 patients, taking into account a loss to follow-up of <5%.
All patients recruited will be provided full explanation of the study and written voluntary consents will be obtained before randomization.
All data will be prospectively collected by dedicated research assistant and computerized into a database. All statistical analysis will be performed with Statistical Product and Service Solution (SPSS) version 24. Missing information will be marked and significant missing data will be excluded from analysis. Chi-square test will be used to compare discrete variables and student T test or Mann Whitney U test for continuous variables. P value less than 0.05 will be considered statistically significant.
Personal data will be obtained by principal investigator and dedicated research assistant to allow analysis of the results. These data will be anonymous, only identified by the first three letters of patient's name. The file will be encrypted and stored in the study institution. All the information will be solely for research purpose and kept strictly confidential.
Research subjects will be provided with phone contacts for any questions or emergency related to the study.
- Conditions
- Breast Cancer, Sentinel Lymph Node
- Being tested
- sentinel lymph node biopsy procedure
- Keywords
- superparamagnetic iron oxide, sentinel lymph node detection rate
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sentinel lymph node biopsy procedureProcedure or surgery
Patient received respective tracer injection and sentinel lymph node biopsy was performed in the operation theatre with the corresponding device.
| Study group | Role | What they receive |
|---|---|---|
| SPIO arm | Experimental | Superparamagnetic iron oxide guided sentinel lymph node mapping Receives: Procedure: sentinel lymph node biopsy procedure |
| Control arm | Active comparator | Conventional radioisotope and blue dye guided sentinel lymph node mapping Receives: Procedure: sentinel lymph node biopsy procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
sentinel lymph node detection rate per patient
Successful sentinel lymph node localization for each arm
Measured: At the time of operation
Secondary outcomes (4)
Number of sentinel lymph nodes detected
Number of sentinel lymph nodes detected in each arm
Measured: At the time of operation
Duration of sentinel lymph node biopsy
Duration of sentinel lymph node biopsy procedure in each arm
Measured: Duration of the operation from incision of axillary fascia to satisfactory nodal basin count
Detection rate of pathologically involved sentinel lymph nodes
Detection rate of malignant sentinel lymph nodes in each arm
Measured: At operation
Duration of skin stain
Duration of blue stain (from blue dye) and brown stain (from SPIO) in respective arm
Measured: post-operative 3 month, 6 month, 12 month and 18 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2022
- Study start24 Jul 2018
- Primary completion29 Feb 2024 (estimated)
- Study completion30 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 282 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, MAN Chi Mei Vivian, The University of Hong Kong
- Investigators
- Ava Kwong, Professor, Study director, university
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05288686
- Sponsor's protocol ID
- HKUCTR-2709
- Status last verified
- May 2023
- First submitted
- 10 Mar 2022
- Last updated
- 10 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Douek M, Klaase J, Monypenny I, Kothari A, Zechmeister K, Brown D, Wyld L, Drew P, Garmo H, Agbaje O, Pankhurst Q, Anninga B, Grootendorst M, Ten Haken B, Hall-Craggs MA, Purushotham A, Pinder S; SentiMAG Trialists Group. Sentinel node biopsy using a magnetic tracer versus standard technique: the SentiMAG Multicentre Trial. Ann Surg Oncol. 2014 Apr;21(4):1237-45. doi: 10.1245/s10434-013-3379-6. Epub 2013 Dec 10.
PubMed 24322530Thill M, Kurylcio A, Welter R, van Haasteren V, Grosse B, Berclaz G, Polkowski W, Hauser N. The Central-European SentiMag study: sentinel lymph node biopsy with superparamagnetic iron oxide (SPIO) vs. radioisotope. Breast. 2014 Apr;23(2):175-9. doi: 10.1016/j.breast.2014.01.004. Epub 2014 Jan 29.
PubMed 24484967Pinero-Madrona A, Torro-Richart JA, de Leon-Carrillo JM, de Castro-Parga G, Navarro-Cecilia J, Dominguez-Cunchillos F, Roman-Santamaria JM, Fuster-Diana C, Pardo-Garcia R; Grupo de Estudios Senologicos de la Sociedad Espanola de Patologia Mamaria (SESPM). Superparamagnetic iron oxide as a tracer for sentinel node biopsy in breast cancer: A comparative non-inferiority study. Eur J Surg Oncol. 2015 Aug;41(8):991-7. doi: 10.1016/j.ejso.2015.04.017. Epub 2015 May 12.
PubMed 25997792Rubio IT, Diaz-Botero S, Esgueva A, Rodriguez R, Cortadellas T, Cordoba O, Espinosa-Bravo M. The superparamagnetic iron oxide is equivalent to the Tc99 radiotracer method for identifying the sentinel lymph node in breast cancer. Eur J Surg Oncol. 2015 Jan;41(1):46-51. doi: 10.1016/j.ejso.2014.11.006. Epub 2014 Nov 15.
PubMed 25466980Houpeau JL, Chauvet MP, Guillemin F, Bendavid-Athias C, Charitansky H, Kramar A, Giard S. Sentinel lymph node identification using superparamagnetic iron oxide particles versus radioisotope: The French Sentimag feasibility trial. J Surg Oncol. 2016 Apr;113(5):501-7. doi: 10.1002/jso.24164. Epub 2016 Jan 12.
PubMed 26754343Ghilli M, Carretta E, Di Filippo F, Battaglia C, Fustaino L, Galanou I, Di Filippo S, Rucci P, Fantini MP, Roncella M. The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment. Eur J Cancer Care (Engl). 2017 Jul;26(4). doi: 10.1111/ecc.12385. Epub 2015 Sep 14.
PubMed 26365441Karakatsanis A, Christiansen PM, Fischer L, Hedin C, Pistioli L, Sund M, Rasmussen NR, Jornsgard H, Tegnelius D, Eriksson S, Daskalakis K, Warnberg F, Markopoulos CJ, Bergkvist L. The Nordic SentiMag trial: a comparison of super paramagnetic iron oxide (SPIO) nanoparticles versus Tc(99) and patent blue in the detection of sentinel node (SN) in patients with breast cancer and a meta-analysis of earlier studies. Breast Cancer Res Treat. 2016 Jun;157(2):281-294. doi: 10.1007/s10549-016-3809-9. Epub 2016 Apr 27.
PubMed 27117158Chiu HY, Man V, Suen D, Kwong A. Skin-Staining From Superparamagnetic Iron Oxide (SPIO) for Sentinel Lymph Node Sampling-Follow-Up Results From a Randomized Trial. World J Surg. 2026 Jan;50(1):21-28. doi: 10.1002/wjs.70173. Epub 2025 Nov 22.
PubMed 41273311
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Superparamagnetic Iron Oxide (SPIO) Versus Conventional Radioisotope and Patent Blue Dye in Sentinel Lymph Node Detection for Breast Cancer: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05288686
- Acronym / sponsor ID
- HKUCTR-2709
- Conditions
- Breast Cancer, Sentinel Lymph Node
- Keywords
- superparamagnetic iron oxide, sentinel lymph node detection rate
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 282 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 24 Jul 2018 (actual)
- Primary completion
- 29 Feb 2024 (estimated)
- Study completion
- 30 Jun 2024 (estimated)
- First posted
- 21 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sentinel lymph node biopsy is mandatory during breast cancer operation for disease staging and treatment. The localization of sentinel lymph node is by the injection of radioisotope and blue dye, which is the gold standard. However the use of radioisotope and blue dye are associated with specific drawbacks. Superparamagnetic iron oxide is a magnetic tracer which is FDA-approved for sentinel lymph node localization. The hypothesis of this study is superparamagnetic iron oxide can replace the conventional dual mapping of radioisotope and blue dye in the detection of sentinel lymph nodes for early breast cancers.
Detailed description
Sentinel lymph node biopsy has replaced axillary dissection as the standard of care in clinically node negative breast cancer. Lymphatic mapping with radioisotope and blue dye were most studied tracer agents and their combination was shown to give the highest nodal identification rate and lowest false negative rate. However the use of radioisotope is strictly monitored due to its radioactivity and blue dye is associated with potential allergic reactions and skin tattoo. Superparamagnetic iron oxide is non-radioactive. It gives an audible signal with the magnetometer and a brown color as visual cue. It has demonstrated comparable nodal identification rate with the conventional method in multiple non-inferiority trials in Europe and the USA. There was no randomized controlled trial for a head-to-head comparison between these mapping technique. The hypothesis of this study is superparamagnetic iron oxide alone can replace the conventional dual mapping of radioisotope and blue dye.
Previous literature suggested the nodal detection rate for conventional method and SPIO was around 97%. Assuming a non-inferiorly limit of 5%, with a power of 80% and 5% significance level, the number of patients per treatment arm should be 144. We will need a sample size of 300 patients, taking into account a loss to follow-up of <5%.
All patients recruited will be provided full explanation of the study and written voluntary consents will be obtained before randomization.
All data will be prospectively collected by dedicated research assistant and computerized into a database. All statistical analysis will be performed with Statistical Product and Service Solution (SPSS) version 24. Missing information will be marked and significant missing data will be excluded from analysis. Chi-square test will be used to compare discrete variables and student T test or Mann Whitney U test for continuous variables. P value less than 0.05 will be considered statistically significant.
Personal data will be obtained by principal investigator and dedicated research assistant to allow analysis of the results. These data will be anonymous, only identified by the first three letters of patient's name. The file will be encrypted and stored in the study institution. All the information will be solely for research purpose and kept strictly confidential.
Research subjects will be provided with phone contacts for any questions or emergency related to the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SPIO arm | Experimental | Procedure: sentinel lymph node biopsy procedureSuperparamagnetic iron oxide guided sentinel lymph node mapping |
| Control arm | Active comparator | Procedure: sentinel lymph node biopsy procedureConventional radioisotope and blue dye guided sentinel lymph node mapping |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- All patients with clinical T1-3N0 invasive ductal carcinoma or invasive lobular carcinoma planned for breast conservative surgery or mastectomy, with sentinel lymph node biopsy
- Patients planned for upfront operation or neoadjuvant chemotherapy are allowed
Key exclusion criteria (5 listed)
- Patients with hypersensitivity to dextran compounds, iron or blue dye
- Patients with iron overload disease
- Pregnant or lactating patients
- Patients with pacemaker or other implantable metallic devices in chest wall or prosthesis in shoulder
- Mentally incompetent patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sentinel lymph node biopsy procedurePatient received respective tracer injection and sentinel lymph node biopsy was performed in the operation theatre with the corresponding device. | Procedure or surgery | Control arm, SPIO arm |
Primary outcome
sentinel lymph node detection rate per patient
Time frame: At the time of operation
Successful sentinel lymph node localization for each arm
4 secondary outcomes
Number of sentinel lymph nodes detected
Time frame: At the time of operation
Duration of sentinel lymph node biopsy
Time frame: Duration of the operation from incision of axillary fascia to satisfactory nodal basin count
Detection rate of pathologically involved sentinel lymph nodes
Time frame: At operation
Duration of skin stain
Time frame: post-operative 3 month, 6 month, 12 month and 18 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Results publication: PubMed 24322530Douek M, Klaase J, Monypenny I, Kothari A, Zechmeister K, Brown D, Wyld L, Drew P, Garmo H, Agbaje O, Pankhurst Q, Anninga B, Grootendorst M, Ten Haken B, Hall-Craggs MA, Purushotham A, Pinder S; SentiMAG Trialists Group. Sentinel node biopsy using a magnetic tracer versus standard technique: the SentiMAG Multicentre Trial. Ann Surg Oncol. 2014 Apr;21(4):1237-45. doi: 10.1245/s10434-013-3379-6. Epub 2013 Dec 10.
- Results publication: PubMed 24484967Thill M, Kurylcio A, Welter R, van Haasteren V, Grosse B, Berclaz G, Polkowski W, Hauser N. The Central-European SentiMag study: sentinel lymph node biopsy with superparamagnetic iron oxide (SPIO) vs. radioisotope. Breast. 2014 Apr;23(2):175-9. doi: 10.1016/j.breast.2014.01.004. Epub 2014 Jan 29.
- Results publication: PubMed 25997792Pinero-Madrona A, Torro-Richart JA, de Leon-Carrillo JM, de Castro-Parga G, Navarro-Cecilia J, Dominguez-Cunchillos F, Roman-Santamaria JM, Fuster-Diana C, Pardo-Garcia R; Grupo de Estudios Senologicos de la Sociedad Espanola de Patologia Mamaria (SESPM). Superparamagnetic iron oxide as a tracer for sentinel node biopsy in breast cancer: A comparative non-inferiority study. Eur J Surg Oncol. 2015 Aug;41(8):991-7. doi: 10.1016/j.ejso.2015.04.017. Epub 2015 May 12.
- Results publication: PubMed 25466980Rubio IT, Diaz-Botero S, Esgueva A, Rodriguez R, Cortadellas T, Cordoba O, Espinosa-Bravo M. The superparamagnetic iron oxide is equivalent to the Tc99 radiotracer method for identifying the sentinel lymph node in breast cancer. Eur J Surg Oncol. 2015 Jan;41(1):46-51. doi: 10.1016/j.ejso.2014.11.006. Epub 2014 Nov 15.
- Results publication: PubMed 26754343Houpeau JL, Chauvet MP, Guillemin F, Bendavid-Athias C, Charitansky H, Kramar A, Giard S. Sentinel lymph node identification using superparamagnetic iron oxide particles versus radioisotope: The French Sentimag feasibility trial. J Surg Oncol. 2016 Apr;113(5):501-7. doi: 10.1002/jso.24164. Epub 2016 Jan 12.
- Results publication: PubMed 26365441Ghilli M, Carretta E, Di Filippo F, Battaglia C, Fustaino L, Galanou I, Di Filippo S, Rucci P, Fantini MP, Roncella M. The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment. Eur J Cancer Care (Engl). 2017 Jul;26(4). doi: 10.1111/ecc.12385. Epub 2015 Sep 14.
- Results publication: PubMed 27117158Karakatsanis A, Christiansen PM, Fischer L, Hedin C, Pistioli L, Sund M, Rasmussen NR, Jornsgard H, Tegnelius D, Eriksson S, Daskalakis K, Warnberg F, Markopoulos CJ, Bergkvist L. The Nordic SentiMag trial: a comparison of super paramagnetic iron oxide (SPIO) nanoparticles versus Tc(99) and patent blue in the detection of sentinel node (SN) in patients with breast cancer and a meta-analysis of earlier studies. Breast Cancer Res Treat. 2016 Jun;157(2):281-294. doi: 10.1007/s10549-016-3809-9. Epub 2016 Apr 27.
- Derived from this study: PubMed 41273311Chiu HY, Man V, Suen D, Kwong A. Skin-Staining From Superparamagnetic Iron Oxide (SPIO) for Sentinel Lymph Node Sampling-Follow-Up Results From a Randomized Trial. World J Surg. 2026 Jan;50(1):21-28. doi: 10.1002/wjs.70173. Epub 2025 Nov 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ava Kwong, Professor study director
university
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing sentinel lymph node biopsy procedure in people with Breast Cancer and Sentinel Lymph Node, run by The University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
sentinel lymph node detection rate per patient (time frame: At the time of operation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05288686, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023.