Use of Superparamagnetic Iron Oxide (SPIO) in Sentinel Lymph Node Detection for Breast Cancer

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05288686
• Other study ID #: HKUCTR-2709
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 24, 2018
• Est. completion date: June 30, 2024

Study information

• Verified date: May 2023
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 282
• Est. completion date: June 30, 2024
• Est. primary completion date: February 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Sentinel Lymph Node

Intervention

Procedure:
• sentinel lymph node biopsy procedure
Patient received respective tracer injection and sentinel lymph node biopsy was performed in the operation theatre with the corresponding device.

Locations

Country	Name	City	State
Hong Kong	University of Hong Kong	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (7)

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 magn — View Citation

Ghilli 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 (Eng — View Citation

Houpeau 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;11 — View Citation

Karakatsanis 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 (S — View Citation

Pinero-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). — View Citation

Rubio 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 — View Citation

Thill 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: 10.10 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	sentinel lymph node detection rate per patient	Successful sentinel lymph node localization for each arm	At the time of operation
Secondary	Number of sentinel lymph nodes detected	Number of sentinel lymph nodes detected in each arm	At the time of operation
Secondary	Duration of sentinel lymph node biopsy	Duration of sentinel lymph node biopsy procedure in each arm	Duration of the operation from incision of axillary fascia to satisfactory nodal basin count
Secondary	Detection rate of pathologically involved sentinel lymph nodes	Detection rate of malignant sentinel lymph nodes in each arm	At operation
Secondary	Duration of skin stain	Duration of blue stain (from blue dye) and brown stain (from SPIO) in respective arm	post-operative 3 month, 6 month, 12 month and 18 month