Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer
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|ClinicalTrials.gov Identifier: NCT04759911|
Recruitment Status : Recruiting
First Posted : February 18, 2021
Last Update Posted : January 26, 2023
|Condition or disease||Intervention/treatment||Phase|
|Malignant Thyroid Gland Neoplasm Poorly Differentiated Thyroid Gland Carcinoma Recurrent Thyroid Gland Carcinoma Thyroid Gland Anaplastic Carcinoma Thyroid Gland Medullary Carcinoma Thyroid Gland Papillary Carcinoma Thyroid Gland Squamous Cell Carcinoma||Other: Quality-of-Life Assessment Other: Questionnaire Administration Drug: Selpercatinib Procedure: Therapeutic Conventional Surgery||Phase 2|
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]).
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.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Neoadjuvant Treatment With Selpercatinib in RET-Altered Thyroid Cancers|
|Actual Study Start Date :||February 26, 2021|
|Estimated Primary Completion Date :||September 10, 2024|
|Estimated Study Completion Date :||September 10, 2024|
Experimental: Treatment (selpercatinib)
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.
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Procedure: Therapeutic Conventional Surgery
Undergo standard of care surgery
- Objective response rate (ORR) [ Time Frame: Up to 7 months ]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.
- Tumor response [ Time Frame: Up to 7 months ]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.
- R0/R1 resection rates [ Time Frame: During surgery ]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.
- Progression free survival (PFS) [ Time Frame: Up to 2 years post treatment ]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.
- Locoregional PFS [ Time Frame: Up to 2 years post treatment ]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 [ Time Frame: Baseline to the date of surgery, assessed up to 7 months ]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.
- Overall survival (OS) [ Time Frame: Up to 5 years post treatment ]Defined as the time from patient registration to death from any causes.
- Incidence of adverse events [ Time Frame: Up to 7 months ]Assessed as defined by Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.
- Quality of life [ Time Frame: Up to 2 years post treatment ]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)].
- Patient-reported outcomes [ Time Frame: Up to 2 years post treatment ]Measured by the M.D. Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) instrument.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04759911
|Contact: Mark Zafereoemail@example.com|
|United States, Michigan|
|University of Michigan Health Systems||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Francis Worden, MD 734-615-6633 firstname.lastname@example.org|
|Principal Investigator: Francis Worden, MD|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Mark Zafereo 713-563-9683|
|Principal Investigator: Mark Zafereo|
|Principal Investigator:||Mark Zafereo||M.D. Anderson Cancer Center|