Symptoms and General Pathology

All Conditions

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Gland and Hormone Related Diseases

Rare Diseases

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Thyroid Neoplasms

Thyroid Cancer, Papillary

Carcinoma, Papillary

Thyroid Diseases

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Thyroid Carcinoma, Anaplastic

Carcinoma, Medullary

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Endocrine System Diseases

Endocrine Gland Neoplasms

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Adenocarcinoma

Neoplasms, Nerve Tissue

Adenocarcinoma, Papillary

Papillary Thyroid Carcinoma

Anaplastic Thyroid Cancer

Thyroid Cancer, Medullary

Neuroendocrine Tumor

Neuroepithelioma

Patients receive selpercatinb PO BID on days 1-28. Treatment repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.

Quality-of-Life Assessment

Questionnaire Administration

Selpercatinib

Therapeutic Conventional Surgery

Mark Zafereo

Francis Worden, MD

This phase II trial studies the effect of selpercatinib given before surgery in treating patients with thyroid cancer whose tumors have RET alterations (changes in the genetic material \[deoxyribonucleic acid (DNA)\]). Selpercatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving selpercatinib before surgery may help shrink the tumors and help control the disease.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of neoadjuvant selpercatinib in medullary thyroid cancer by objective response rate (ORR) per RECIST (standard Response Evaluation Criteria in Solid Tumors \[RECIST\]).

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of neoadjuvant selpercatinib in medullary thyroid cancer by ORR per modified neck RECIST.

II. To evaluate the efficacy of neoadjuvant selpercatinib in medullary thyroid cancer per surgical margin status, which is categorized as R0, R1, and R2 surgical resection.

III. To evaluate the safety profile of neoadjuvant selpercatinib.

IV. To evaluate the efficacy of neoadjuvant selpercatinib on progression-free survival (PFS), including overall PFS and locoregional PFS.

V. To measure changes in expected and actual surgical morbidity/complexity as well as evaluate changes of R0/R1 resection rates in pre-specified extrathyroidal anatomic target interfaces before and after selpercatinib treatment.

EXPLORATORY OBJECTIVES:

I. In patients with differentiated thyroid cancer \[DTC\] and anaplastic thyroid cancer \[ATC\] only, to evaluate the efficacy of neoadjuvant selpercatinib by ORR per RECIST (standard RECIST and modified neck RECIST), surgical margin status (R0/R1 versus \[vs.\] R2), safety profile, surgical morbidity/complexity, PFS and overall survival (overall survival \[OS\], ATC only).

II. To define and measure changes of patient-reported outcomes and quality of life as measured by MD Anderson Symptom Inventory (MDASI) and European Quality of Life Five Dimension (EQ-5D) in patients with RET-altered thyroid cancer who receive selpercatinib treatment.

III. To explore translational endpoints in selpercatinib neoadjuvant therapy with biopsies/tissue collection before selpercatinib treatment and during surgery.

IV. To explore peripheral and tissue measures associated with selpercatinib mechanisms of resistance in patients who experience disease progression after selpercatinib treatment.

OUTLINE:

Patients receive selpercatinb orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.

After completion of study treatment, patients are followed up for disease progression status every 3-4 months for the first 2 years. ATC patients continue follow-up every 6 months for year 3 and 4, and once in year 5.

Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer

Neoadjuvant Treatment With Selpercatinib in RET-Altered Thyroid Cancers

Defined as the percentage of number of complete response or partial response in total number of patients treated. With ORR by Response Evaluation Criteria in Solid Tumors (RECIST), will report the percentages of patients that fall into each of the four categories: complete response, partial response, stable disease or progressive disease according to RECIST 1.1.

Assessed using modified neck RECIST, which applies the RECIST criteria only to lesions above the clavicles. Will report the percentages of patients that fall into each of the four categories: complete response, partial response, stable disease or progressive disease according to modified neck RECIST 1.1.

Defined by proportion of patients who undergo successful thyroidectomy with clear (R0) or microscopically positive (R1) surgical margins. Will evaluate R0/R1 resection rates in each of 4 pre-specified extrathyroidal anatomic target interfaces: 1) perithyroid muscles (e.g. strap, sternocleidomastoid, inferior constrictor muscles) 2) cartilage (larynx/trachea) 3) esophagus 4) recurrent laryngeal nerve.

Defined as the time from patient registration to disease progression or death from any cause. Structural progression is defined according to RECIST criteria based on histopathologic findings, and biochemical progression is defined as abnormal thyroglobulin (Tg) or rising Tg antibody levels for anaplastic thyroid cancer/differentiated thyroid cancer, and abnormal carcinoembryonic antigen/calcitonin for medullary thyroid cancer.

Defined as the time from patient registration to locoregional progression or death from any cause. Locoregional progression is defined as disease progression above the clavicles according to modified neck RECIST criteria.

Surgical morbidity/complexity score will be measured at enrollment, prior to surgery and at surgery. The Thyroid Neck Group Morbidity Complexity Scoring and MGH/MEE-MSK-MD Anderson (MMM) Surgical Morbidity Complexity Score are incorporated, specifying on scale with 5 levels of complexity and mobidity of the surgery \[mild (level 0), moderate (level 1), severe (level 2), very severe (level 3), and unresectable (level 4)\]. The surgical morbidity/complexity scores will be collected at enrollment, prior to surgery and at surgery; descriptive statistics such as means and standard deviations will be calculated for each time point.

Defined as the time from patient registration to death from any causes.

Assessed as defined by Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.

Assessed by the European Quality of Life 5 Dimension Questionnaire (EQ-5D). The EQ-5D consists of health state description and evaluation. The health state description consists of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), with each dimension specifying five levels of severity \[best (1)-worst (5)\]. The health state evaluation is assessed using the visual analogue scale (\[worse (0)-best (100)\].

Measured by the M.D. Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) instrument.

M.D. Anderson Cancer Center

Thyroid Nodule

Potentially cancerous thyroid nodules were assessed by elastrography, then a fine needle biopsy specimen or the surgically-excised nodule was assessed pathologically to determine cancer status.

Siemens Acuson S3000 ultrasound system

Aya Kamaya

This clinical trial studies how well ultrasound elastography works in assessing the cancer status of potentially malignant thyroid nodules.

PRIMARY OBJECTIVES:

Determine the utility of ultrasound elastography in evaluation of thyroid nodules being evaluated for the presence of cancer.

Elastography measures the passages of ultrasound shear waves through tissue to gauge the stiffness and compressibility of the tissue, collectively "tissue stiffness," and may be a better way to image thyroid nodules. Tissue stiffness is a physiological parameter that is being evaluated for differences between non-cancerous (benign) and cancerous thyroid nodules.

Participants will undergo elastography over the 10 minutes prior to either fine needle aspiration of a biopsy specimen or surgical resection of the thyroid nodule. Tissue specimens from the biopsy specimen or surgical resection will be assessed pathologically to determine actual cancer status.

Ultrasound Elastography in Imaging Patients With Thyroid Nodules

Elastography in Thyroid Nodule Evaluation

Potentially cancerous thyroid nodules will be assessed elastographically, and cancer status will be determined from a fine needle aspiration biopsy results or the surgically excised nodule. The outcome will be reported as median tissue stiffness with standard deviation for nodules that were determined non-cancerous (benign), cancerous, or indeterminate.

Stanford University

Professor of Radiology

Potentially cancerous thyroid nodules were assessed by elastrography, then a fine needle biopsy specimen or the surgically-excised nodule was assessed pathologically to determine cancer status.

Siemens Acuson S3000 ultrasound system: Shear Wave Elastography

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer	NCT04759911	Malignant Thyro... Poorly Differen... Recurrent Thyro... Thyroid Gland A... Thyroid Gland M... Thyroid Gland P... Thyroid Gland S...	Quality-of-Life... Questionnaire A... Selpercatinib Therapeutic Con...	12 Years -	M.D. Anderson Cancer Center
Ultrasound Elastography in Imaging Patients With Thyroid Nodules	NCT03174925	Malignant Thyro... Thyroid Gland N...	Siemens Acuson ...	18 Years -	Stanford University
Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer	NCT04759911	Malignant Thyro... Poorly Differen... Recurrent Thyro... Thyroid Gland A... Thyroid Gland M... Thyroid Gland P... Thyroid Gland S...	Quality-of-Life... Questionnaire A... Selpercatinib Therapeutic Con...	12 Years -	M.D. Anderson Cancer Center
Ultrasound Elastography in Imaging Patients With Thyroid Nodules	NCT03174925	Malignant Thyro... Thyroid Gland N...	Siemens Acuson ...	18 Years -	Stanford University

Spots Global Cancer Trial Database for malignant thyroid gland neoplasm