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Trial Title:
Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer
NCT ID:
NCT05783323
Condition:
Differentiated Thyroid Cancer
Pediatric Cancer
Cancer
Cancer, Thyroid
Conditions: Official terms:
Thyroid Neoplasms
Thyroid Diseases
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Larotrectinib monotherapy
Description:
Patients will receive larotrectinib monotherapy for 6 months at the FDA-approved dose.
Arm group label:
Larotrectinib monotherapy with 131I therapy
Intervention type:
Radiation
Intervention name:
131I therapy
Description:
Patients will receive 131I therapy after 6 months of larotrectinib.
Arm group label:
Larotrectinib monotherapy with 131I therapy
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.
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.
Criteria for eligibility:
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 or 131I.
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.
Gender:
All
Minimum age:
2 Years
Maximum age:
99 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Children's Hospital of Philadelphia
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shelby Brizzolara-Dove
Email:
22DT025@chop.edu
Investigator:
Last name:
Theodore Laetsch, MD
Email:
Principal Investigator
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Luz Castellanos, MD
Phone:
713-792-2841
Email:
LECastellanos@mdanderson.org
Start date:
February 14, 2024
Completion date:
October 1, 2027
Lead sponsor:
Agency:
Children's Hospital of Philadelphia
Agency class:
Other
Collaborator:
Agency:
Bayer
Agency class:
Industry
Source:
Children's Hospital of Philadelphia
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05783323
