Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer

Eligibility Criteria

• 1. Age ≥ 1 year
• 2. 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
• 3. Anatomically evaluable disease on chest CT meeting one of the following criteria (obtained within 90 days of enrollment):
• 4. 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
• 5. Lansky/Karnofsky performance status ≥ 50%
• 6. Adequate Organ 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).
• * Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age.
• * Serum glutamic-pyruvic transaminase (SGPT) (ALT) ≤ 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
• * Serum albumin ≥ 2 g/dL
• 7. Female patients of reproductive potential must agree to use a highly effective contraceptive method for the duration of study therapy and for at least one month after the final dose of larotrectinib. Males of reproductive potential with a non-pregnant female partner of child-bearing potential must use a highly effective contraception for the duration of the study and for at least one month after the final dose of larotrectinib.
• 1. No prior systemic therapy for thyroid cancer, including tropomyosin receptor kinase (TRK) inhibitors or 131I.
• 2. Females who are pregnant or breastfeeding are excluded due to the potential risks of larotrectinib and RAI to the fetus/neonate.
• 3. 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.