Precision Thyroid Cancer Surgery With Molecular Fluorescent Guided Imaging

NCT ID: NCT03470259

Last Updated: 2024-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-20
• Study Completion Date: 2019-12-31

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

Conditions

Papillary Thyroid Cancer; Lymph Node Metastases

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

EMI-137 0.09mg/kg administration

Three patients will be once administered with EMI-137 0.09 mg/kg. Thereafter the patient will be observed for an hour. Two hours after injection surgery will be performed and only ex-vivo imaging and spectroscopy will be performed of thyroid glands and lymph nodes with a multispectral Near Infrared Fluorescence (NIRF) camera system and spectroscopy system.

After interim analysis will be decided if this dosage group has an adequate tumor-to-background ratio and dose extension will be performed.

Group Type: EXPERIMENTAL

IV adminstration of EMI-137

Intervention Type: DRUG

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

Multispectral Fluorescence Reflectance Imaging

Intervention Type: DEVICE

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

Intervention Type: DEVICE

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.

EMI-137 0.13mg/kg administration

Three patients will be once administered with EMI-137 0.13 mg/kg. Thereafter the patient will be observed for an hour. Two hours after injection surgery will be performed and only ex-vivo imaging and spectroscopy will be performed of thyroid glands and lymph nodes with a multispectral Near Infrared Fluorescence (NIRF) camera system and spectroscopy system.

After interim analysis will be decided if this dosage group has an adequate tumor-to-background ratio and dose extension will be performed.

Group Type: EXPERIMENTAL

IV adminstration of EMI-137

Intervention Type: DRUG

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

Multispectral Fluorescence Reflectance Imaging

Intervention Type: DEVICE

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

Intervention Type: DEVICE

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.

EMI-137 0.18mg/kg administration

Three patients will be once administered with EMI-137 0.18 mg/kg. Thereafter the patient will be observed for an hour. Two hours after injection surgery will be performed and only ex-vivo imaging and spectroscopy will be performed of thyroid glands and lymph nodes with a multispectral Near Infrared Fluorescence (NIRF) camera system and spectroscopy system.

After interim analysis will be decided if this dosage group has an adequate tumor-to-background ratio and dose extension will be performed.

Group Type: EXPERIMENTAL

IV adminstration of EMI-137

Intervention Type: DRUG

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

Multispectral Fluorescence Reflectance Imaging

Intervention Type: DEVICE

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

Intervention Type: DEVICE

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.

EMI-137 0.045mg/kg administration

If we have a excellent tumor to background ratio ((tumor fluorescence)/(surrounding tissue fluorescence)) in the 0.09 mg/kg group, we will de-escalate back to a 0.045 mg/kg group to evaluate TBR and reduce possible tracer toxicity in a thyroid cancer population with 90% 20 year survival.

Three patients will be once administered with EMI-137 0.045 mg/kg. Thereafter the patient will be observed for an hour. Two hours after injection surgery will be performed and only ex-vivo imaging and spectroscopy will be performed of thyroid glands and lymph nodes with a multispectral Near Infrared Fluorescence (NIRF) camera system and spectroscopy system.

After interim analysis will be decided if this dosage group has an adequate tumor-to-background ratio and dose extension will be performed.

Group Type: EXPERIMENTAL

IV adminstration of EMI-137

Intervention Type: DRUG

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

Multispectral Fluorescence Reflectance Imaging

Intervention Type: DEVICE

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

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DEVICE

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.

Intervention Type: DEVICE

Other Intervention Names

IMP administration; MFRI

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Erasmus Medical Center

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Schelto Kruijfff, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Gooitzen M van Dam, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Center Groningen

Groningen, , Netherlands

Erasmus Medical Center

Rotterdam, , Netherlands

Countries

Netherlands

References

Metman MJH, Jonker PKC, Sondorp LHJ, van Hemel BM, Sywak MS, Gill AJ, Jansen L, van Diest PJ, van Ginhoven TM, Lowik CWGM, Nguyen AH, Robinson DJ, van Dam GM, Links TP, Coppes RP, Fehrmann RSN, Kruijff S. MET-receptor targeted fluorescent imaging and spectroscopy to detect multifocal papillary thyroid cancer. Eur J Nucl Med Mol Imaging. 2024 Jul;51(8):2384-2394. doi: 10.1007/s00259-023-06525-5. Epub 2023 Nov 29.

Reference Type: DERIVED

PMID: 38017325 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35389070 (View on PubMed)

Other Identifiers

NL62817.042.17

Identifier Type: -

Identifier Source: org_study_id