Clinical trial NCT03470259: Precision Thyroid Cancer Surgery With Molecular Fluorescent Guided Imaging
Official title: Detection of Thyroid Cancer and Central Lymph Node Metastases Using EMI-137 Enhanced Molecular Fluorescent Guided Imaging: a Multicentre Feasibility and
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Papillary Thyroid Cancer
Lymph Node Metastases
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
First posted: 2018-03-19
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: See brief summary

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years, eligible for surgery
2. Bethesda VI fine needle aspiration (FNA) thyroid or FNA proven PTC metastasis (primary or recurrence).
3. Scheduled to undergo central and/or lateral lymph node dissection with or without thyroidectomy as discussed in the Multi-Disciplinary Thyroid Board.
4. WHO performance score of 0-2.
5. Written informed consent.
6. Mentally competent person who is able and willing to comply with study procedures.
7. For female subjects who are of childbearing potential are premenopausal with intact reproductive organs or are less than two years post-menopausal:

   * A negative serum pregnancy test prior to receiving the tracer
   * Willing to ensure that she or her partner uses effective contraception during the trial and for 3 months thereafter.

Exclusion Criteria:

1. Pregnancy or breast feeding
2. Advanced stage thyroid cancer not suitable for surgical resection
3. Medical or psychiatric conditions that compromise the patient's ability to give informed consent
4. Concurrent anticancer therapy (chemotherapy, radiotherapy, vaccines, immunotherapy) delivered within the last three months prior to the start of the treatment
5. The subject has been included previously in this study or has been injected with another investigational medicinal product within the past six months
6. History of myocardial infarction (MI), TIA, CVA, pulmonary embolism, uncontrolled congestive heart failure (CHF), significant liver disease, unstable angina within 6 months prior to enrollment
7. Any significant change in their regular prescription or non-prescription medication between 14 days and 1 day prior to IMP administration.

Primary outcomes:
measure: The feasibility of Molecular Fluorescence Guided Surgery using EMI-137
timeFrame: From tracer administration until after data analyses which will take up to 1.5year
Secondary outcomes:
measure: Safety of using EMI-137 through monitoring vital signs
timeFrame: 1 day
measure: Safety of using EMI-137 through monitoring injection site
timeFrame: 1 day
measure: Feasibility of MFGS for detecting nodal metastasis
timeFrame: Up to one year
measure: Feasibility of spectroscopy for detecting fluorescence of PTC and lymph nodes
timeFrame: Up to one year
measure: Validation of flourescence
timeFrame: Up to one year
measure: Distribution of EMI-137
timeFrame: Up to 1.5 year
measure: Sensitivity and specificity of EMI-137
timeFrame: Up to 1.5 year
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
Study officials:
affiliation: University Medical Center Groningen
name: Schelto Kruijfff, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: Gooitzen M van Dam, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jonker PKC, Metman MJH, Sondorp LHJ, Sywak MS, Gill AJ, Jansen L, Links TP, van Diest PJ, van Ginhoven TM, Lowik CWGM, Nguyen AH, Coppes RP, Robinson DJ, van Dam GM, van Hemel BM, Fehrmann RSN, Kruijff S. Intraoperative MET-receptor targeted fluorescent imaging and spectroscopy for lymph node detection in papillary thyroid cancer: novel diagnostic tools for more selective central lymph node compartment dissection. Eur J Nucl Med Mol Imaging. 2022 Aug;49(10):3557-3570. doi: 10.1007/s00259-022-05763-3. Epub 2022 Apr 7.