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

NCT04759911 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-0570NCI-2021-00535
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Objective response rate (ORR)

  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.

  Up to 7 months

• Tumor response

  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.

  Up to 7 months

Secondary Outcomes (8)

• R0/R1 resection rates

  During surgery

• Progression free survival (PFS)

  Up to 2 years post treatment

• Locoregional PFS

  Up to 2 years post treatment

• Surgical morbidity/complexity score

  Baseline to the date of surgery, assessed up to 7 months

• Overall survival (OS)

  Up to 5 years post treatment

Study Arms (1)

Treatment (selpercatinib)

EXPERIMENTAL

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: Questionnaire Administration; Drug: Selpercatinib; Procedure: Therapeutic Conventional Surgery

Interventions

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (selpercatinib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (selpercatinib)

Selpercatinib DRUG

Given PO

Also known as: LOXO-292, RET Kinase Inhibitor LOXO-292, Retevmo, WHO 10967

Treatment (selpercatinib)

Therapeutic Conventional Surgery PROCEDURE

Undergo standard of care surgery

Treatment (selpercatinib)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with RET-altered thyroid cancer who present with locally advanced primary tumor, defined as T3 or T4 by imaging or invasive/bulky nodal disease, or with recurrent/residual invasive/bulky nodal disease will be enrolled in this trial, regardless of whether distant metastases are present or not
• At least 12 years of age on the day of signing informed consent
• Pathologic findings supporting the clinical impression of medullary thyroid carcinoma, papillary thyroid carcinoma, poorly differentiated thyroid carcinoma, or anaplastic thyroid carcinoma. Diagnosis of anaplastic thyroid carcinoma may include consistent with or suggestive of terminology associated with: anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous carcinoma; carcinoma with spindled, giant cell, or epithelial features; poorly differentiated carcinoma with pleomorphism, extensive necrosis with tumor cells present
• Having an activating RET gene alteration (fusion or mutation). The RET alteration result should be generated from a laboratory with Clinical Laboratory Improvement Act (CLIA), ISO/EIC, College of American Pathologists (CAP), or other similar certification that clearly denotes the presence of a RET alteration in tumor, or institutional-approved cell free DNA blood test for RET alteration
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed. The specific agent(s), duration of treatment, clinical benefit, and reason for discontinuation (e.g., progressive disease \[PD\], drug toxicity, or intolerance) should be documented for all kinase inhibitors the patient has been exposed to
• At least one measurable lesion as defined by RECIST 1.1
• Surgical morbidity/complexity score of 1 to 4 (moderate, severe, very severe, or unresectable)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (age \>= 16 years) or Lansky Performance Score (LPS) \>= 40% (age \< 16 years) with no sudden deterioration 2 weeks prior to study registration
• Absolute neutrophil count (ANC) \>= 1500/uL
• Hemoglobin \>= 9 g/dL (5.58 mmol/L)
• Platelets \>= 100,000/uL
• Total bilirubin =\< 1.5 X upper limit of normal (ULN) (Except participants with a documented history of Gilbert syndrome who must have a total bilirubin \< 3 X ULN)
• Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) \< 2.5 X ULN OR \< 5 X ULN if the liver has tumor involvement
• Normal serum potassium, calcium, and magnesium levels (may be receiving supplements). Grade 1 hypocalcemia (corrected serum calcium \> 8) is acceptable
• Willing to undergo tumor biopsy prior to trial treatment, unless in the opinion of the treating physician, a biopsy is not feasible or safe. Subjects must be willing to ultimately undergo surgery if their tumor becomes surgically resectable

You may not qualify if:

• An additional validated oncogenic driver that could cause resistance to selpercatinib treatment (if known)
• Prior treatment with a selective RET inhibitor(s) (pralsetinib \[BLU-667\], including investigational selective RET inhibitor\[s\])
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, or immunotherapy) within 5 half-lives or 3 weeks (whichever is shorter) prior to planned start of selpercatinib
• Exception: Patients with ATC
• No concurrent investigational anti-cancer therapy is permitted
• Major surgery (excluding placement of vascular access and diagnostic procedures) within 4 weeks prior to planned start of selpercatinib
• Exception: Patients with ATC
• Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum therapy related neuropathy
• Symptomatic primary central nervous system (CNS) tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression
• Exception: Patients are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of selpercatinib and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
• Patients with clinically significant active cardiovascular disease, Torsades de pointes, or history of myocardial infarction within 6 months prior to planned start of study treatment or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 470 msec
• Patients with clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the drug
• Use of a concomitant medication that is known to cause QTc prolongation
• Active uncontrolled systemic bacterial, viral, or fungal infection, or serious ongoing intercurrent illness, such as uncontrolled hypertension (systolic blood pressure \[BP\] \>= 140 mmHg or diastolic BP \>= 90 mmHg per CTCAE) or diabetes, despite optimal treatment. Screening for chronic conditions is not required

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (3)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

University of Michigan Health Systems

Ann Arbor, Michigan, 48109, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Thyroid Neoplasms; Thyroid Carcinoma, Anaplastic; Carcinoma, Medullary; Thyroid Cancer, Papillary

Interventions

selpercatinib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Adenocarcinoma; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue; Adenocarcinoma, Papillary

Study Officials

• Mark Zafereo

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 18, 2021
• Study Start: February 26, 2021
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: November 13, 2025

Record last verified: 2025-11

Locations

US (3)