The Role of 68-Gallium-DOTATATE-PET/CT in the Imaging of Metastatic Thyroid Cancer

Study Description:

The study is designed to identify the patients with metastatic radioactive iodine (RAI) non-avid or non-responsive thyroid cancer, whose tumors are characterized by the high expression of somatostatin receptors type 2 (SSTR2) by imaging with 68Gallium(68Ga)-DOTATATE Positron Emission Tomography/Computed Tomography (PET/CT). Participants will undergo a one-time experimental imaging with 68Ga-DOTATATE PET/CT. This imaging will enable identification of patients with high maximum standard uptake value (SUVmax) of 68Ga-DOTATATE defined as SUVmax of >15, as this SUVmax threshold has been associated with a good response to peptide receptor radionuclide therapy (PRRT) in pre-clinical and clinical models of SSTR2-positive tumors. PRRT will not be offered in this trial.

Objectives:

Primary Objective:

To compare the prevalence of patients with metastatic RAI-non-avid or RAI-non-responsive thyroid cancer whose tumors are characterized by a high SSTR2 expression by imaging with 68Ga-DOTATATE PET/CT between three groups:

• Group HTC--the molecularly and histologically unique subtype of differentiated thyroid cancer (DTC) - Hurthle cell thyroid cancer (HTC),
• Group DTC--patients with remaining histological types of DTC,
• Group MTC--patients with metastatic thyroid cancer of neuroendocrine origin - medullary thyroid cancer (MTC).

Secondary Objectives:

• To analyze the association between the 68Ga-DOTATATE uptake and molecular signature of thyroid cancer and tumor volume,
• to create a repository of data for future research in thyroid cancer.

Endpoints:

Primary Endpoint: Prevalence of thyroid cancer patients characterized by a high SSTR2 expression in at least one metastatic lesions per patient documented by SUVmax of 68Ga-DOTATATEPET/CT of above 15 among patients with metastatic HTC, DTC and MTC.

Secondary Endpoints: Associations between 68Ga-DOTATATE uptake as measured by SUVmax in up to 10 lesions per organ per patient and:

• Somatic mutation status in primary tumors divided into BRAF-like, RAS-like, harboring mitochondrial DNA mutations and /or RET protooncogene mutation,
• Tumor volume measured in cm3 per the ellipsoid formula p/6 length*width*depth.

• INCLUSION CRITERIA:

Data prospectively collected from the 28 subjects enrolled under this protocol, and data from 26 subjects collected under 77-DK-0096 and/or 00-CH-0093 will be analyzed. Among the 26 subjects prospectively evaluated under 77-DK-0096 protocol, 21 out of 26 had research 68Ga-DOTATATE PET/CT performed under the DOTATATE sub-study of 77-DK-0096, and 5 out of 26 had 68Ga-DOTATATE PET/CT done under 00-CH-0093. Again, the inclusion of the above data was per the IRB s request to transition the sub-study into a new standalone protocol. This will give us a total of 54 subjects for the final analyses, with at least 18 subjects from each group (e.g., HTC, DTC, and MTC), which is required to meet the primary objectives of this study with sufficient power of 80% and type 1 error alpha of < 0.05.

Patients with HTC, DTC, and MTC will be identified by the investigators. The potential candidates for the study will be screened for eligibility to participate in the study and invited to sign the Research 68Ga-DOTATATE PET/CT imaging informed consent form. The same inclusion/exclusion criteria were applied to the subjects who underwent imaging with the 68GADOTATATE PET/CT, either under the 77-DK-0096 sub-study or as clinically-indicated imaging under 00-CH-0093.

In order to be eligible to participate in this study, an individual with DTC (including HTC) must meet all of the following criteria:

• Male or female, aged >18 years.
• Patients with established thyroid cancer diagnosis presenting with either:

• Locally advanced or distant metastases, which are RAI-non-avid based on the or diagnostic or post-treatment whole body scan (WBS)

OR

--Patients with RAI-non-responsive disease, who have the evidence of disease progression defined by RECIST 1.1 criteria after therapy with RAI.

In order to be eligible to participate in this study, an individual with MTC must meet all of the following criteria:

• Male or female, aged >18 years.
• Patients with locally advanced or metastatic MTC or patients suspected of locally advanced or metastatic MTC with calcitonin level > 500 pg/mL.

Exclusion criteria

Subjects with either HTC, DTC, or MTC who meet any of the following criteria will be excluded from participation in this study:

• Pregnancy or lactation by self-report.
• Serious underlying medical conditions that restrict diagnostic testing or therapy such as renal failure, congestive cardiac failure or active coexisting non-thyroid carcinoma;
• Patients unable to give informed consent.