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Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer

NCT ID: NCT05783323

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-14

Study Completion Date

2027-10-01

Brief Summary

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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

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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.

Conditions

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Differentiated Thyroid Cancer Pediatric Cancer Cancer Cancer, Thyroid

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Larotrectinib monotherapy with 131I therapy

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.

Group Type EXPERIMENTAL

Larotrectinib monotherapy

Intervention Type DRUG

Patients will receive larotrectinib monotherapy for 6 months at the FDA-approved dose.

131I therapy

Intervention Type RADIATION

Patients will receive 131I therapy after 6 months of larotrectinib.

Interventions

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Larotrectinib monotherapy

Patients will receive larotrectinib monotherapy for 6 months at the FDA-approved dose.

Intervention Type DRUG

131I therapy

Patients will receive 131I therapy after 6 months of larotrectinib.

Intervention Type RADIATION

Eligibility Criteria

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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.
Minimum Eligible Age

2 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Theodore Laetsch, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

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University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Seattle Children's Hospital

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Meghan Donnelly

Role: CONTACT

Phone: 267-426-9343

Email: [email protected]

James Robinson

Role: CONTACT

Phone: 215-590-2053

Email: [email protected]

Facility Contacts

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Arun Rangaswami, MD

Role: primary

Meghan Donnelly

Role: primary

Sara Helmig, MD

Role: primary

Luz Castellanos, MD

Role: primary

Tyler Ketterl, MD, MS

Role: primary

Other Identifiers

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22-020549

Identifier Type: -

Identifier Source: org_study_id