Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer

Sponsor

Theodore Laetsch (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05783323

Collaborator

Bayer (Industry)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Differentiated Thyroid Cancer Pediatric Cancer Cancer Cancer, Thyroid	Drug: Larotrectinib monotherapy Radiation: 131I therapy	Phase 2

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

Study Type:

Interventional

Anticipated Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

Larotrectinib to Enhance RAI Avidity in Patients With Differentiated Thyroid Cancer Harboring NTRK Fusions

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Larotrectinib monotherapy Patients will receive larotrectinib monotherapy for 6 months at the FDA-approved dose. Radiation: 131I therapy Patients will receive 131I therapy after 6 months of larotrectinib.

Arm

Intervention/Treatment

Experimental: 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.

Drug: Larotrectinib monotherapy

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

Radiation: 131I therapy

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

Outcome Measures

Primary Outcome Measures

Number of patients with complete pulmonary structural response [18 months]
The primary endpoint is the complete pulmonary structural response rate to larotrectinib by modified Nies et al thyroid cancer response criteria.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 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 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%
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

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.

Exclusion Criteria

No prior systemic therapy for thyroid cancer, including tropomyosin receptor kinase (TRK) inhibitors or 131I.
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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Theodore Laetsch
Bayer

Investigators

Principal Investigator: Theodore Laetsch, MD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Theodore Laetsch, Director, Developmental Therapeutics, Children's Hospital of Philadelphia

ClinicalTrials.gov Identifier:

NCT05783323

Other Study ID Numbers:

22-020549

First Posted:

Mar 24, 2023

Last Update Posted:

Mar 24, 2023

Last Verified:

Mar 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Thyroid Neoplasms

Thyroid Diseases

Study Results

No Results Posted as of Mar 24, 2023