Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer

Prior treatment

• No prior systemic therapy for thyroid cancer, including tropomyosin receptor kinase (TRK) inhibitors. Note that prior 131I is permitted.
• 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.

Other

• Females who are pregnant or breastfeeding are excluded due to the potential risks of larotrectinib and RAI to the fetus/neonate.

• 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):
  • 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
  • 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).
  • 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
  • Adequate Liver Function
  • 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
• 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.