An official website of the United States government
Government Funding Lapse Because of a lapse in government funding, the information on this website may not be up to date, transactions submitted via the website may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted.
The NIH Clinical Center (the research hospital of NIH) is open. For more details about its operating status, please visit cc.nih.gov.
Updates regarding government operating status and resumption of normal operations can be found at opm.gov.
Larotrectinib with Radioactive Iodine for the Treatment of Patients with Metastatic Differentiated Thyroid Cancer with NTRK Fusions, LANTERN Trial
Trial Status: active
This phase II trial studies how well larotrectinib and radioactive iodine work for the treatment of patients with differentiated thyroid cancer with NTRK fusions that has spread from where it first started (primary site) to other places in the body (metastatic). Larotrectinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive iodine treatment with iodine I-131 involves the patients taking a large dose of radioactive iodine, which kills thyroid cells. Giving larotrectinib before radioactive iodine treatment may work better for treating patients with metastatic differentiated thyroid cancer with NTRK fusions.
Inclusion Criteria
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 computed tomography (CT) meeting one of the following criteria (obtained within 90 days of enrollment):
* Multiple (> 10) noncalcified solid pulmonary nodules visible on CT and/or
* Enlarging, discrete pulmonary nodules visible on CT of any number consistent with metastatic disease
Identification of an NTRK1, NTRK2, or NTRK3 gene fusion in a Clinical Laboratory Improvement Act (CLIA)/College of American Pathologists (CAP) accredited laboratory without known kinase domain resistance mutation
Platelet count ≥ 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
Hemoglobin ≥ 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)
Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m^2 or a maximum serum creatinine based on age/gender
* 1 to < 2 years: Maximum serum creatinine 0.6 mg/dL (male), 0.6 mg/dL (female)
* 2 to < 6 years: Maximum serum creatinine 0.8 mg/dL (male), 0.8 mg/dL (female)
* 6 to < 10 years: Maximum serum creatinine 1 mg/dL (male), 1 mg/dL (female)
* 10 to < 13 years: Maximum serum creatinine 1.2 mg/dL (male), 1.2 mg/dL (female)
* 13 to < 16 years: Maximum serum creatinine 1.5 mg/dL (male), 1.5 mg/dL (female)
* >= 16 years: Maximum serum creatinine 1.7 mg/dL (male),1.7 mg/dL (female)
Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [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
Exclusion Criteria
Prior systemic therapy for thyroid cancer, including tropomyosin receptor kinase (TRK) inhibitors or 131 I
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
Additional locations may be listed on ClinicalTrials.gov for NCT05783323.
I. To evaluate the structural response rate within 18 months to the combination of larotrectinib given for 6-months followed by iodine I-131 (131I) therapy (in patients without complete response at 6 months) in patients with NTRK fusion differentiated thyroid cancer.
SECONDARY OBJECTIVES:
I. To determine the overall, structural, and biochemical response rate to larotrectinib in patients with NTRK fusion differentiated thyroid cancer treated with 6 months of larotrectinib prior to 131I therapy.
II. To determine the progression free survival to the combination of larotrectinib followed 6 months later by 131I therapy from the initiation of larotrectinib therapy.
III. To determine the proportion of patients for whom oncogene-specific, targeted therapy increases tumor radioactive iodine (RAI)-avidity.
IV. To determine the safety of the combination of larotrectinib given for 6-months followed by 131I therapy in patients with NTRK fusion differentiated thyroid cancer.
V. To evaluate the influence of baseline disease characteristics, specific NTRK gene fusions and concurrent genetic alterations on changes in RAI-avidity and efficacy of the combination of larotrectinib followed by 131I therapy.
OUTLINE:
Patients receive larotrectinib orally (PO) or via nasogastric or gastrostomy tube twice per day (BID) for up to 6 months in the absence of unacceptable toxicity. At month 6 or disease progression, patients receive standard of care RAI treatment with iodine I-131. Patients continue taking larotrectinib until 5 days after completion of RAI treatment. Patients may consume a low iodine diet for 7-14 days, receive thyrogen intramuscularly (IM) and radioactive sodium iodine PO and undergo a whole body scan on study.
After completion of study treatment, patients are followed up every 3 months for up to 18 months after study entry and then every 6 months for up to 5 years after study entry.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationChildren's Hospital of Philadelphia
