Differentiated Thyroid CancerPhase 2NCT05783323
Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer
A Phase 2 study testing Larotrectinib monotherapy and 131I therapy in people with Differentiated Thyroid Cancer and Pediatric Cancer, run by Children's Hospital of Philadelphia at 6 sites in United States.
Trial summary
Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid cancer (DTC). The traditional first line treatment for patients with advanced DTC after surgical resection is radioactive iodine (RAI) therapy. Read more about this study
- Who is it for?
- Ages 2 to 99 years
- Conditions the study is for
- Differentiated Thyroid Cancer, Pediatric Cancer, Cancer
- What is being tested?
- Larotrectinib monotherapy and 131I therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 6 sitesUnited States
- Study dates
- 14 Feb 2024to 1 Oct 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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%
Show all 20Show fewer
- 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.
Who cannot join
- No prior systemic therapy for thyroid cancer, including tropomyosin receptor kinase (TRK) inhibitors. Note that prior 131I is permitted.
- 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.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
United States6 sites, 6 recruiting
- Not yet recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Junne Kamihara, MD, Junne_Kamihara@dfci.harvard.edu
Junne Kamihara, MD
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Luz Castellanos, MD, 713-792-2841, LECastellanos@mdanderson.org
- Recruiting
St. Jude Children's Research Hospital
Memphis, Tennessee, 19807
Sara Helmig, MD, 901-593-3300, Sara.Helmig@stjude.org
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Meghan Donnelly, 267-426-9343, 22DT025@chop.edu
Theodore Laetsch, MD
- Recruiting
University of California, San Francisco
San Francisco, California, 94115
Arun Rangaswami, MD, arun.rangaswami@ucsf.edu
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Tyler Ketterl, MD, MS
About this study
Official title: Larotrectinib to Enhance RAI Avidity in Patients With Differentiated Thyroid Cancer Harboring NTRK Fusions (LANTERN)
Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid cancer (DTC). The traditional first line treatment for patients with advanced DTC after surgical resection is radioactive iodine (RAI) therapy. However, less than a quarter of patients with lung metastases will achieve a complete response to RAI therapy, and this therapy carries the risk of pulmonary fibrosis and an increasingly recognized risk of secondary malignancies.
Read the detailed description
This is an open label, non-randomized study to evaluate the efficacy and safety of the combination of larotrectinib followed by 131I therapy for patients with NTRK fusion differentiated thyroid cancer. The primary Phase II objective will be to evaluate the pulmonary structural response rate at 18 months to the combination of larotrectinib given for 6-months followed by 131I therapy.
- Being tested
- Larotrectinib monotherapy, 131I therapy
- Medical subject headings
- Neoplasms, Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Larotrectinib monotherapyDrug
Patients will receive larotrectinib monotherapy for 6 months at the FDA-approved dose.
131I therapyRadiation
Patients will receive 131I therapy after 6 months of larotrectinib.
| Study group | Role | What they receive |
|---|---|---|
| Larotrectinib monotherapy with 131I therapy | Experimental | Patients will receive larotrectinib monotherapy for 6 months at the FDA-approved dose.
Patients will receive 131I therapy after 6 months of larotrectinib. Larotrectinib will be continued for 5 days after RAI therapy and then patients will enter a wait and see period off treatment.
Patients who experience disease progression at any point while on larotrectinib will proceed to 131I therapy and discontinue larotrectinib. Receives: Drug: Larotrectinib monotherapy; Radiation: 131I therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with complete pulmonary structural response
The primary endpoint is the complete pulmonary structural response rate to larotrectinib by modified Nies et al thyroid cancer response criteria.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2023
- Study start14 Feb 2024
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Differentiated Thyroid CancerStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This will be an open label, non-randomized study to evaluate the efficacy and safety of the combination of larotrectinib followed by 131I therapy for patients with NTRK fusion differentiated thyroid cancer.
- Masking
- None (open label)
- Enrolment
- 13 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Theodore Laetsch, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05783323
- Sponsor's protocol ID
- 22-020549
- Status last verified
- Oct 2026
- First submitted
- 2 Mar 2023
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Larotrectinib to Enhance RAI Avidity in Patients With Differentiated Thyroid Cancer Harboring NTRK Fusions (LANTERN)
- ClinicalTrials.gov ID
- NCT05783323
- Acronym / sponsor ID
- 22-020549
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 13 participants (estimated)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- 14 Feb 2024 (actual)
- Primary completion
- 1 Oct 2028 (estimated)
- Study completion
- 1 Oct 2030 (estimated)
- First posted
- 24 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid cancer (DTC). The traditional first line treatment for patients with advanced DTC after surgical resection is radioactive iodine (RAI) therapy. However, less than a quarter of patients with lung metastases will achieve a complete response to RAI therapy, and this therapy carries the risk of pulmonary fibrosis and an increasingly recognized risk of secondary malignancies.
Detailed description
This is an open label, non-randomized study to evaluate the efficacy and safety of the combination of larotrectinib followed by 131I therapy for patients with NTRK fusion differentiated thyroid cancer. The primary Phase II objective will be to evaluate the pulmonary structural response rate at 18 months to the combination of larotrectinib given for 6-months followed by 131I therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This will be an open label, non-randomized study to evaluate the efficacy and safety of the combination of larotrectinib followed by 131I therapy for patients with NTRK fusion differentiated thyroid cancer.
| Arm | Type | Receives |
|---|---|---|
| Larotrectinib monotherapy with 131I therapy | Experimental | Drug: Larotrectinib monotherapy, Radiation: 131I therapyPatients will receive larotrectinib monotherapy for 6 months at the FDA-approved dose. Patients will receive 131I therapy after 6 months of larotrectinib. Larotrectinib will be continued for 5 days after RAI therapy and then patients will enter a wait and see period off treatment. Patients who experience disease progression at any point while on larotrectinib will proceed to 131I therapy and discontinue larotrectinib. |
Who may qualify
- Ages
- 2 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (20 listed)
- 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):
- 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%
Key exclusion criteria (3 listed)
- No prior systemic therapy for thyroid cancer, including tropomyosin receptor kinase (TRK) inhibitors. Note that prior 131I is permitted.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Larotrectinib monotherapyPatients will receive larotrectinib monotherapy for 6 months at the FDA-approved dose. | Drug | Larotrectinib monotherapy with 131I therapy |
| 131I therapyPatients will receive 131I therapy after 6 months of larotrectinib. | Radiation | Larotrectinib monotherapy with 131I therapy |
Primary outcome
Number of patients with complete pulmonary structural response
Time frame: 18 months
The primary endpoint is the complete pulmonary structural response rate to larotrectinib by modified Nies et al thyroid cancer response criteria.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Theodore Laetsch, MD principal investigator
Children's Hospital of Philadelphia
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Larotrectinib monotherapy and 131I therapy in people with Differentiated Thyroid Cancer and Pediatric Cancer, run by Children's Hospital of Philadelphia at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Meghan Donnelly (267-426-9343, donnellymt@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with complete pulmonary structural response (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.