Using Larotrectinib to Improve Radioactive Iodine Treatment in Thyroid Cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This open-label, non-randomized Phase II study aims to evaluate the efficacy and safety of combining larotrectinib with radioactive iodine (RAI) therapy for patients with differentiated thyroid cancer that has NTRK gene fusions. Participants will receive larotrectinib for six months, followed by RAI therapy, with the primary objective being to assess the pulmonary structural response rate at 18 months. The study focuses on patients who have undergone surgical resection and have evaluable metastatic disease. The goal is to enhance the effectiveness of RAI therapy, particularly for those with lung metastases.

Why it matters

Who can join: the full rules

Inclusion 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):

   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
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

   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

   C. 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
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.

Exclusion Criteria

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

Where it's running

• University of California, San Francisco
  San Francisco, California, United States Recruiting
• Children's Hospital of Philadelphia
  Philadelphia, Pennsylvania, United States Recruiting
• St. Jude Children's Research Hospital
  Memphis, Tennessee, United States Recruiting
• MD Anderson Cancer Center
  Houston, Texas, United States Recruiting
• Seattle Children's Hospital
  Seattle, Washington, United States Recruiting
• Dana-Farber Cancer Institute
  Boston, Massachusetts, United States Not yet recruiting

Study contacts

• Principal investigator: Theodore Laetsch, MD — Children's Hospital of Philadelphia
• Study coordinator: Meghan Donnelly
• Email: donnellymt@chop.edu
• Phone: 267-426-9343

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.