Precision Thyroid Cancer Surgery With Molecular Fluorescent Guided Imaging

Lymph Node Metastases Clinical Trial

— TARGET  

Official title:

Detection of Thyroid Cancer and Central Lymph Node Metastases Using EMI-137 Enhanced Molecular Fluorescent Guided Imaging: a Multicentre Feasibility and

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03470259
• Other study ID #: NL62817.042.17
• Status: Completed
• Phase: Phase 1
• Start date: June 20, 2018
• Est. completion date: December 31, 2019

Study information

• Verified date: April 2024
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

See brief summary

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymph Node Metastases
• Lymphatic Metastasis
• Neoplasm Metastasis
• Papillary Thyroid Cancer
• Thyroid Cancer, Papillary
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• IV adminstration of EMI-137
Intravenous administration of the fluorescent tracer EMI-137 approximately two hours before incision. Thereafter will be an observational period of an hour.

Device:
• Multispectral Fluorescence Reflectance Imaging
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.
• Spectroscopy
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.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Erasmus Medical Center	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The feasibility of Molecular Fluorescence Guided Surgery using EMI-137	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.	From tracer administration until after data analyses which will take up to 1.5year
Secondary	Safety of using EMI-137 through monitoring vital signs	To evaluate the safety of EMI-137 through monitoring vital signs for evaluating possible (severe) adverse events.	1 day
Secondary	Safety of using EMI-137 through monitoring injection site	To evaluate the safety of EMI-137 through monitoring the injection site for evaluating possible (severe) adverse events.	1 day
Secondary	Feasibility of MFGS for detecting nodal metastasis	To evaluate the feasibility of MFGS for the assessment of PTC and nodal metastasis by calculating target-to-background ratio.	Up to one year
Secondary	Feasibility of spectroscopy for detecting fluorescence of PTC and lymph nodes	To determine the feasibility of ex vivo spectroscopy measurements of PTC and lymph nodes for quantification of the fluorescence signal of EMI-137	Up to one year
Secondary	Validation of flourescence	To correlate and validate fluorescence signals detected ex vivo with histopathology and immunohistochemistry by determining if high flourescence areas show tumorcells in pathological examination.	Up to one year
Secondary	Distribution of EMI-137	To evaluate the distribution of EMI-137 on a microscopic level using fluorescence microscopy.	Up to 1.5 year
Secondary	Sensitivity and specificity of EMI-137	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.	Up to 1.5 year