Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05375526 |
| Other study ID # |
NL75863.068.21 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2022 |
| Est. completion date |
October 1, 2024 |
Study information
| Verified date |
May 2022 |
| Source |
Maastricht University Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Epithelial ovarian cancer (EOC) remains the tumour with the most unfavourable prognosis
within the field of gynaecological oncology. The incidence of ovarian cancer in the
Netherlands in 2008 was 14.5 per 100.000, with 12.3 deaths per 100.000. In the US in 2007 the
incidence was 13.0 per 100.000 and there were 8.2 deaths per 100.000. The high mortality rate
is partially due to the fact that approximately 75% of patients is diagnosed with advanced
stage EOC. The remaining 25% of patients are diagnosed in an early stage, which require a
complete surgical staging procedure including pelvic and para-aortic lymphadenectomy.
Although this lymphadenectomy is standard-of-care, it leads to significant morbidity in these
patients. Mainly direct postoperative complications such as infection, repeat surgery and
early death have been reported. Also, long-term complications such as lymph cysts or
lymphedema have been described.
A potential method to reduce this morbidity and mortality, as already been described in other
cancers such as breast cancer and vulvar cancer, is utilizing a sentinel lymph node (SLN)
technique. By identifying and resecting the SLN, the patient is potentially spared form
lymphadenectomy.
Description:
Background EOC can metastasize through three different pathways: intraperitoneal (in the
abdominal cavity), lymphogenous or haematogenous [5,6]. Concerning the lymphogenous spread,
it is clear that lymphatic spread of EOC occurs mainly to the para-aortic lymph nodes. It is
theorized that the tumour cells follow the lymph vessels that accompany the ovarian vessels
in the infundibulopelvic ligament up to the upper para-aortic region and renal vein.
Additionally, pelvic lymph node metastases are also frequently found. These tumour cells
probably follow a different route, migrating via the para-uterine vessels in the broad
ligament towards the uterine vessels and further on to the iliac vessels and lymph nodes. In
some case reports, isolated inguinal node metastases are also described. The exact mechanism
of this route of metastasis is still unclear, but the metastatic cells might follow the
course of the round ligament towards the inguinal lymph nodes or follow the iliac vessels
towards the femoral vessels.
According to the International Federation of Gynaecology and Obstetrics (FIGO), EOC with
lymph node metastases is classified as FIGO stage IIIA1. This significant upstaging is
reflected in the need for adjuvant treatment. While patients with cancer confined to the
ovaries (FIGO stage I) do not require adjuvant chemotherapy, patients with EOC FIGO stage III
require additional treatment. Therefore, the detection of lymph node metastases is of utmost
importance in perceived early stage disease.
In case of a clinical early stage ovarian cancer, standard-of-care is a staging laparotomy
including bilateral pelvic and para-aortal lymphadenectomy. There is 14% (range 6.1-29.6%)
chance of finding lymph node metastases . The incidence is higher in the grade 3 tumours
(20.0%) and the serous histological subtype (23.3%). Whereas in grade 1 and mucinous tumours
this is respectively 4.0% and 2.6%. By removing a greater number of lymph nodes, the
detection rate for metastases rises . Although complete pelvic and para-aortic
lymphadenectomy is standard-of-care, radical lymphadenectomy has been associated with serious
morbidity and this is a major reason for the difference in the extent of lymph node
dissection between centres.
By resecting only the SLN, significant reduction of morbidity and mortality can be obtained
in comparison with the standard-of-care. SLN surgery is based on the concept that, if the SLN
has no malignant cells, the likelihood that other lymph nodes are affected is reduces to
almost non-existent. This means that, at least theoretically, a radical lymphadenectomy could
be omitted and thus the associated morbidity and potential mortality. The SLN technique has
been proven to be effective in other cancers such as breast cancer and malignant melanoma. In
the gynaecological field it has been shown to be effective in vulvar cancer. Several SLN
studies have been conducted in patients with ovarian cancer with promising results, as
summarized in Table 1.
Rationale As stated, the goal of utilizing SLN in early-stage EOC surgery is to reduce
patient morbidity while obtaining optimal oncological outcomes. By resecting only the SLN,
the patients would be spared from radical lymphadenectomy, reducing short and long-term
complications.
As summarized in Table 1, most studies utilize 99mTc and blue dye to visualize the SLN.
Although detection rates are good with these techniques, they have major disadvantages. 99mTC
is an isotope, as such it exposed the patient to an irradiation dose. Although total dosage
is limited, eliminating isotopes in surgery would reduce the potential harm for the patient
and the medical staff during surgery. Furthermore, the process to produce and administer
99mTC is a costly and resource-intensive procedure, requiring the cooperation of nuclear
medicine, radio-pharmacy and logistics. As such, reducing the need for 99mTc would benefit
the patient, medical staff and the healthcare system in general by reducing costs. Blue dye
such as Patent Blue is often used for the detection of SLN. However, it also has major
disadvantages. Firstly, it potentially occludes the entire operation field because of
dissemination of the dye further than the SLN. Without optimal visualisation of the anatomy,
the surgeon can expect more difficult dissection. Secondary, blue dye can cause a severe
allergic reaction, leading to anaphylactic shock in up to 2% of patients.
Magtrace® is a brownish ferromagnetic substance capable of identifying the SLN. This novel
technique has already been extensively researched in breast cancer and proven to be
non-inferior to 99mTc with blue dye. These promising results led to licensing in the European
Union. In this trial, the investigators wish to examine the potential of this technique in
EOC, eliminating the disadvantages of 99mTc and blue dye. However, this is still a pilot
study with unknown efficacy in EOC. Therefore, in order to minimize potential harm to the
patient, 99mTc will be co administrated. This has been deliberately chosen due to the
extensive literature concerning this sentinel mapping technique (see Table 1). If the
efficacy of Magtrace would prove successful, the ultimate goal is to omit 99mTc in further
studies and use Magtrace® only to identify the SLN.
In this pilot study, researchers will include two study arms. One in primary staging
laparotomy, the other one in secondary staging laparotomy. The rationale of these two arms is
based on the clinical practice, were surgeons not always suspect malignancy before resection
of the adnexa. In case of a primary staging laparotomy the diagnosis of malignancy is based
on a frozen section of the resected adnexa, followed by the sentinel node technique during
the same procedure. On the other hand, in some cases early stage EOC is only diagnosed after
the primary surgery, when the surgeon resects the ovary with the suspicion of benign disease.
If the adnexa are already removed before the diagnosis of malignancy, a secondary staging
laparotomy is required and, in this case, a single step approach for SLN is not feasible. The
design of two study arms in this pilot study allows to compare the efficacy of Magtrace in
native tissue (primary staging laparotomy) with tissue afflicted by previous surgery
(secondary staging laparotomy).
