Selpercatinib Pre-RAI in Patients With RET Fusion Thyroid Cancer (RAISE)

NCT06458036 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-021524
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 4

Brief Summary

Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid cancer (DTC). The traditional first line treatment for patients with advanced DTC after surgical resection is radioactive iodine (RAI) therapy. However, less than a quarter of patients with lung metastases will achieve a complete response to RAI therapy, and this therapy carries the risk of pulmonary fibrosis and an increasingly recognized risk of secondary malignancies.

Conditions

Differentiated Thyroid Cancer; Pediatric Cancer; Cancer; Cancer, Thyroid

Keywords

Thyroid Cancer

Outcome Measures

Primary Outcomes (4)

• Number of patients with complete overall, pulmonary, structural, and biochemical response.

  Determine the overall, pulmonary, structural, and biochemical response rate to selpercatinib in patients with RET fusion differentiated thyroid cancer treated with 6 months of selpercatinib prior to 131I therapy

  18 months

• Number of patients who survive without progression of disease after 5 years following protocol treatment.

  Determine the progression free survival to the combination of selpercatinib followed 6 months later 131I therapy from the initiation of selpercatinib therapy

  5 years

• Proportion of all patients enrolled who show increased radioactive iodine avidity at 6 months following selpercatinib monotherapy.

  Determine the proportion of patients for whom oncogene-specific, targeted therapy increases tumor RAI-avidity.

  6 months

• The incidence of adverse events and dose limiting toxicity with the combination of selpercatinib and 131I therapy, graded according to CTCAE v5.

  Determine the safety of the combination of selpercatinib given for 6-months followed by 131I therapy in patients with RET fusion differentiated thyroid cancer

  12 months

Study Arms (1)

Experimental: Selpercatinib Monotherapy with 131I Therapy

EXPERIMENTAL

Patients will receive selpercatinib monotherapy for 6 months at the FDA-approved dose. Patients will receive 131I therapy after 6 months of selpercatinib. Selpercatinib will be continued for 5 days after RAI therapy and then patients will enter a wait and see period off treatment. Patients who experience disease progression at any point while on selpercatinib will proceed to 131I therapy and discontinue selpercatinib.

Drug: Selpercatinib Monotherapy; Radiation: 131I Therapy

Interventions

Selpercatinib Monotherapy DRUG

Patients will receive selpercatinib monotherapy for 6 months at the FDA-approved dose.

Experimental: Selpercatinib Monotherapy with 131I Therapy

131I Therapy RADIATION

Patients will receive 131I therapy after 6 months of selpercatinib.

Experimental: Selpercatinib Monotherapy with 131I Therapy

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 2-25 years, inclusive
• Histologic diagnosis of a differentiated thyroid cancer, status post thyroidectomy and adequate local therapy (e.g., lymph node dissection as per standard of care) for metastatic disease in the neck in the opinion of the treating investigator
• Anatomically evaluable disease on chest CT (Computed Tomography) meeting one of the following criteria (obtained within 90 days of enrollment):
• A. multiple (\> 10) noncalcified solid pulmonary nodules visible on CT and/or B. enlarging, discrete pulmonary nodules visible on CT of any number consistent with metastatic disease
• Identification of an activating RET gene alteration (fusion or mutation). The RET alteration result should be generated from a laboratory with specific certifications (depending on country requirement) that clearly denotes the presence of a RET alteration without known kinase domain resistance mutation
• Lansky/Karnofsky performance status \>50%
• Adequate Organ Function
• A. Bone Marrow Function:
• Peripheral absolute neutrophil count (ANC) ≥1500/µL
• Platelet count ≥ 100,000/µL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Hemoglobin ≥ 9.0 g/dL at baseline (may receive Red Blood Cell transfusions).
• B. Adequate Renal Function: Creatinine clearance or radioisotope Glomerular Filtration Rate (GFR) ≥ 70 mL/min/1.73 m2 or a maximum serum creatinine based on age/gender.
• C. Adequate Liver Function
• Bilirubin (sum of conjugated + unconjugated) \< / = 1.5 x upper limit of normal (ULN) for age. Except participants with a documented history of Gilbert syndrome who must have a total bilirubin level of \<3.0X ULN
• Alanine aminotransferase (ALT) \<2.5X ULN OR \<5x ULN if the liver has tumor involvement. For the purpose of this study, the ULN for ALT is 45 U/L.

You may not qualify if:

• No prior systemic therapy for thyroid cancer, including RET inhibitors. Note: prior 131I is allowed.
• Females who are pregnant or breastfeeding are excluded due to the potential risks of selpercatinib and radioactive iodine to the fetus/neonate.
• Concurrent therapy: Patients currently receiving a strong CYP3A4 inducer or inhibitor are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided 14 days prior to treatment to the end of the study treatment.
• 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.
• Have clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the drug.
• Are taking a concomitant medication that is known to cause QTc prolongation.
• Active hemorrhage or at significant risk for hemorrhage.
• Uncontrolled hypertension (blood pressure greater than 140/90 in adults or greater than the 95% for height and gender in children). Use of anti-hypertensives to control blood pressure is permitted.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• Eli Lilly and Company: collaborator
• United States Department of Defense: collaborator

Study Sites (4)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

NOT YET RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Neoplasms; Thyroid Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Theodore Laetsch, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meghan Donnelly, MPH

CONTACT

267-426-9343; 23DT022@chop.edu

James Robinson

CONTACT

215-590-2053; robinsonj9@chop.edu

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: June 10, 2024
• First Posted: June 13, 2024
• Study Start: July 29, 2024
• Primary Completion (Estimated): November 1, 2030
• Study Completion (Estimated): November 1, 2031
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)