Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03898687 |
| Other study ID # |
DNR 947-18 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2019 |
| Est. completion date |
September 30, 2020 |
Study information
| Verified date |
October 2020 |
| Source |
Sahlgrenska University Hospital, Sweden |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
To evaluate the use of superparamagnetic iron oxide (Magtrace®) as a tracer in sentinel node
biopsy in malignant melanoma of the extremities, and to evaluate the possible role of
Magtrace®-MRI for staging.
Primary objective:
• To evaluate if Magtrace®/Sentimag® can be used to identify SN in malignant melanoma with
the same diagnostically reliability as the currently used method of Technetium 99m and Patent
blue.
Secondary objectives:
• To evaluate if Magtrace®-MRI can predict sentinel node status in melanoma. This is a
feasibility phase I, interventional single arm study. All patients included in the study will
receive the same management.
20 patients will be included in the study. An enrollment time of 6-12 months is expected.
Primary endpoint • To determine the detection rate of Magtrace®/Sentimag® in comparison to
SNB using technetium and blue dye in patients with malignant melanoma of the extremities.
Secondary endpoint
• To evaluate Magtrace®-MRI sensitivity and specificity as a preoperative tool for staging in
malignant melanoma.
Description:
Background Sentinel node biopsy (SNB) is a well-established technique for nodal staging of
malignant disease, including breast cancer and malignant melanoma. The sentinel node (SN) is
the first lymph node to receive cancer cells in a given lymph node basin. The status of the
SN is often the most important prognostic factor, and determines potential adjuvant therapy
and follow-up. The SN is detected by injection of a radioactive isotope (Technetium 99m) and
a blue dye around the tumour or the scar following primary resection. This is achieved by a
lymphoscintigraphy which is usually performed the day before surgery which necessitates a
nuclear medicine department. At the time of surgery, a blue dye (Patent blue) is injected at
the same area prior to incision. Thereafter the SN is identified by a handheld gamma-probe
and the dye which colours the sentinel node blue. The so called hot and blue lymph node is
removed surgically and sent to pathology for staging.
The mortality of cutaneous malignant melanoma is high, especially when diagnosed in an
advanced stage [4]. Accurate staging and prediction of outcome largely depend on the
identification and examination of the SN. SNB is recommended in Sweden for melanomas with a
Breslow thickness more than 1 mm. About 20% of SNs in patients with melanoma are positive,
which affects follow-up and also potentially adjuvant therapies that recently have been
approved.
SNB is a surgical technique with associated risk for complications, mainly seroma, infections
and lymph-edema. If nodal status could be determined by imaging, the dissection of the
sentinel node biopsy could be avoided. However, current imaging techniques, such as MRI, CT
and ultrasound are not accurate enough to stage the lymph nodes preoperatively. Motomura et
al. recently reported a technique where superparamagnetic iron-oxide (SPIO) is injected into
the tumour in patients with breast cancer, followed by MRI scan. They found a 100%
sensitivity and 96% specificity for node staging when being compared to SNB.
There has been an increasing interest in using SPIO for identifying the sentinel node in
breast cancer and recent publications showed great accuracy when SPIO was used as the only
tracer. The agent was injected intra tumoral or subcutaneously under the areola before
surgery and the SN(s) was/were detected by use of a handheld probe (Sentimag, Endomagnetics
Ltd). The Sentimag is a magnetometer, which measures the strength of the magnetic field
created by the iron oxide particles in the SPIO. It is a handheld device that signals when it
is close enough to a magnetic field. The method was compared for feasibility and sensitivity
to the current method used for identifying the SN (Technetium and Patent blue) and it was
found to be at least as reliable and accurate.
Concerning melanoma, the SPIO method has not been used except recently when the MELAMAG trial
was published. SPIO was compared to blue dye and radioisotope for identification of sentinel
node in clinically node negative patients with melanoma. 97.7% of patients had a sentinel
node identified with the standard technique, whereas 95.3% were identified with the magnetic
tracer.
In view of these results, using SPIO as the only tracer to identify the sentinel node, in
melanoma patients, instead of the double technique, could also be feasible. This could also
be combined to SPIO MRI before surgery so as to evaluate this as a non-interventional method.
The primary aim of this study is to evaluate the detection rate of SPIO (Magtrace®) in
patients with melanoma of the extremities compared to technetium and blue dye. The secondary
aim is to evaluate the specificity and sensitivity of SPIO (Magtrace®)-MRI.
STUDY OBJECTIVES AND DESIGN Study Objectives Primary objective
• To evaluate if Magtrace®/Sentimag® can be used to identify SN in malignant melanoma with
the same diagnostically reliability as the currently used method of Technetium 99m and Patent
blue.
Secondary objectives To evaluate if Magtrace®-MRI can predict sentinel node status in
melanoma.
Study design Patients diagnosed with malignant melanoma of the extremities being candidates
for wide local excision and SNB, will be considered for enrollment. Patients should have a
primary melanoma located to one extremity, without clinically suspected lymph nodes
metastasis on palpation and be planned for a SNB. A total of 20 patients that complete the
study will be included. The study will be presented both by verbal and written means by one
of the investigators. If the patient accepts enrolment, a written informed consent will be
signed by both parties.
Patients will undergo an MRI of the lymph node basin (axillary or inguinal). Then they will
receive an interstitial injection of Magtrace® with or without local anaesthesia up to a
total of 2 ml divided in 4 doses injected in 4 quadrants around the previous excision scar.
Care shall be taken for the injection not to exceed the excision area and thus cause a
permanent skin discoloration after the wide local excision. After a minimum of 2 hours a new
MRI (Magtrace®-MRI) of the same lymph node basin will be performed. The surgery will be
scheduled within 7 days from the Magtrace® injection. The results of the Magtrace®-MRI will
be evaluated to decide potential SNs and their status with the radiologist prior to surgery.
The SN will be considered non-metastatic (negative) if it shows homogenous, low intensity
signal on T2 weighted images compared to pre- Magtrace® images. A node will be considered as
metastatic (positive) if the whole node or parts of it does not show a low intensity signal
on T2 weighted image or if there is a high signal on water excitation compared to pre-
Magtrace® images.All SNs identified by MRI will be considered for excision if they can be
identified by using the Sentimag® probe.
A lymphoscintigraphy with Technetium-99m will be performed the day before surgery, in
accordance to our current practice. Results will be investigated thoroughly and compared to
the Magtrace®-MRI results, in order to identify discrepancies between the two methods.
During surgery, the current double technique, with the gamma probe and the blue dye, will be
combined with the Sentimag, Endomagnetics Ltd probe and the intraoperative findings will be
registered and analysed by the investigators, so as to test the feasibility of the method in
comparison to the double method. All the nodes harvested will be sent to pathology and the
final results will be compared to the Magtrace®-MRI results prior to surgery. CRF will be
completed at the end of surgery and then when definitive pathology report is available. Data
from all 20 patients included in this trial will be analysed at the end of the study.
Patients will be followed according to clinical routine, no specific follow-up is required
for this study.
