Using Larotrectinib to Improve Radioactive Iodine Treatment in Thyroid Cancer
Larotrectinib to Enhance RAI Avidity in Patients With Differentiated Thyroid Cancer Harboring NTRK Fusions (LANTERN)
This study is testing if adding a drug called larotrectinib to radioactive iodine treatment can help people with a specific type of thyroid cancer that has spread to the lungs feel better.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 13 (estimated) |
| Ages | 2 Years to 99 Years |
| Sex | All |
| Sponsor | Children's Hospital of Philadelphia Academic / other |
| Drugs / interventions | larotrectinib |
| Locations | 5 sites (San Francisco, California and 4 other locations) |
| Trial ID | NCT05783323 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Ideal candidates include patients aged 1 year and older with histologically confirmed differentiated thyroid cancer and NTRK gene fusions.
Not a fit: Patients without NTRK gene fusions or those with significant comorbidities affecting organ function may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with differentiated thyroid cancer by enhancing the effectiveness of RAI therapy.
How similar studies have performed: While the combination of larotrectinib and RAI therapy is a novel approach, previous studies have shown promise in targeting NTRK fusions in other cancers.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
San Francisco, California and 4 other locations
- 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)
Study contacts
- Principal investigator: Theodore Laetsch, MD — Children's Hospital of Philadelphia
- Study coordinator: Meghan Donnelly
- Email: donnellymt@chop.edu
- Phone: 267-426-9343
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.