Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer

NCT05783323 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-020549
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (1)

• Number of patients with complete pulmonary structural response

  The primary endpoint is the complete pulmonary structural response rate to larotrectinib by modified Nies et al thyroid cancer response criteria.

  18 months

Study Arms (1)

Larotrectinib monotherapy with 131I therapy

EXPERIMENTAL

Patients will receive larotrectinib monotherapy for 6 months at the FDA-approved dose. Patients will receive 131I therapy after 6 months of larotrectinib. Larotrectinib 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 larotrectinib will proceed to 131I therapy and discontinue larotrectinib.

Drug: Larotrectinib monotherapy; Radiation: 131I therapy

Interventions

Larotrectinib monotherapy DRUG

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

Larotrectinib monotherapy with 131I therapy

131I therapy RADIATION

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

Larotrectinib monotherapy with 131I therapy

Eligibility Criteria

• Age: 2 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 1 year
• Histologic diagnosis of a differentiated thyroid cancer, s/p 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 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 neurotrophic tyrosine receptor kinase (NTRK) (NTRK1, NTRK2, or NTRK3) gene fusion in a CLIA/CAP accredited laboratory without known kinase domain resistance mutation
• Lansky/Karnofsky performance status ≥ 50%
• Adequate Organ Function
• A. Bone Marrow Function:
• Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3
• Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Hemoglobin ≥ to 8.0 g/dL at baseline (may receive red blood cell (RBC) 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 as follows:
• Age Maximum Serum Creatinine (mg/dL) Male Female 1 to \< 2 years 0.6 0.6 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1 1 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.5
• ≥ 16 years 1.7 1.7

You may not qualify if:

• No prior systemic therapy for thyroid cancer, including tropomyosin receptor kinase (TRK) inhibitors. Note that prior 131I is permitted.
• Females who are pregnant or breastfeeding are excluded due to the potential risks of larotrectinib and RAI 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.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• Bayer: collaborator

Study Sites (5)

University of California, San Francisco

San Francisco, California, 94115, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 19807, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

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

CONTACT

267-426-9343; donnellymt@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

Model Details: This will be an open label, non-randomized study to evaluate the efficacy and safety of the combination of larotrectinib followed by 131I therapy for patients with NTRK fusion differentiated thyroid cancer.

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: March 24, 2023
• Study Start: February 14, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)