IV adminstration of EMI-137
DrugIntravenous administration of the fluorescent tracer EMI-137 approximately two hours before incision. Thereafter will be an observational period of an hour.
Other names: IMP administration
NCT Number: NCT03470259
Almost 50 % of papillary thyroid cancer (PTC) patients have central lymph node metastases (CLNM), which are associated with a high risk of persistent or recurrent disease. However, the practice of performing a prophylactic central lymph node dissection (PCLND) routinely remains controversial. The proponents argue that without a PCLND, PTC patients with positive lymph nodes have an increased risk of local recurrence, and postponed node dissection leads to with 5-6 fold higher risk of morbidity. If performed, PCLND in clinical node negative patients increases staging to pN1 in more than 50% of the cases without increasing survival. The complication rate in PCLND is lower when compared to a technically challenging re-exploration in recurrent disease, with reported incidences of 0.6% and 7.3-20%, respectively. Opponents of routine PCLND point out the lack of randomized clinical trials and object to treatment-induced hypo-parathyroidism and recurrent nerve damage for the N0 patients. Currently, no diagnostic tool is available which reliably identifies these patient categories. Therefore, there is a clear need for novel diagnostic imaging modalities that overcome this issue. Molecular Fluorescence Guided Surgery (MFGS) is potentially such a diagnostic tool. The administration of NIR fluorescent tracers can increase detection accuracy of cancer and nodal metastatic tissue using macroscopic MFGS. Therefore, we aimed to identify a GMP-produced near infrared (NIR) tracer that potentially has a high target-to-background ratio in PTC compared to normal thyroid tissue. Tyrosine-protein kinase Met (c-Met) is significantly upregulated at the protein level in PTC compared to normal thyroid tissue. The investigators therefore hypothesize that the GMP-produced NIR-fluorescent tracer EMI-137 (targeting c-Met, peak emission at 675 nm range) might be useful for intraoperative imaging of PTC and nodal metastases. The investigators' aim is to investigate if the administration of EMI-137 is a feasible approach to detect PTC nodal metastases. Ultimately, this method might be useful to improve patient selection for CLND. Eventually, we might also be able to visualize multifocality, more selective lateral neck dissections and asses residual tissue after thyroidectomy. Ultimately, all of these strategies may reduce overtreatment, morbidity, and costs while maintaining the same or better effectiveness with a lower recurrence rate and improved quality of life.
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All sexes
Interventional
Phase 1
University Medical Center Groningen, Groningen, Netherlands
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Healthy volunteers accepted: No
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Inclusion criteria
Exclusion criteria
Intravenous administration of the fluorescent tracer EMI-137 approximately two hours before incision. Thereafter will be an observational period of an hour.
Other names: IMP administration
A multispectral Near Infrared Fluorescence (NIRF) camera system sensitive for EMI-137 fluorescence will be used for only ex-vivo Multispectral Fluorescence Reflectance Imaging (MFRI) of the thyroid gland and/or lymph node compartment.
Other names: MFRI
A spectroscopy system sensitive for EMI-137 fluorescence will be used for only ex-vivo spectroscopy of the thyroid gland and/or lymph node compartment.
Time frame: From tracer administration until after data analyses which will take up to 1.5year
To determine the optimal dose of the c-Met targeting NIRF tracer EMI-137 for an adequate TBR in PTC lymph nodes metastases using 3, and possibly 4, different dosages op EMI-137.
Time frame: 1 day
To evaluate the safety of EMI-137 through monitoring vital signs for evaluating possible (severe) adverse events.
Time frame: 1 day
To evaluate the safety of EMI-137 through monitoring the injection site for evaluating possible (severe) adverse events.
Time frame: Up to one year
To evaluate the feasibility of MFGS for the assessment of PTC and nodal metastasis by calculating target-to-background ratio.
Time frame: Up to one year
To determine the feasibility of ex vivo spectroscopy measurements of PTC and lymph nodes for quantification of the fluorescence signal of EMI-137
Time frame: Up to one year
To correlate and validate fluorescence signals detected ex vivo with histopathology and immunohistochemistry by determining if high flourescence areas show tumorcells in pathological examination.
Time frame: Up to 1.5 year
To evaluate the distribution of EMI-137 on a microscopic level using fluorescence microscopy.
Time frame: Up to 1.5 year
To quantify sensitivity and specificity of EMI-137 for PTC and nodal metastasis in order to make a power size calculation for a possible subsequent diagnostic accuracy study.
University Medical Center Groningen
Other
Detection of Thyroid Cancer and Central Lymph Node Metastases Using EMI-137 Enhanced Molecular Fluorescent Guided Imaging: a Multicentre Feasibility and
Acronym: TARGET
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