Larotrectinib for Thyroid Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Theodore W. Laetsch

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Theodore Laetsch

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: Pregnancy, Breastfeeding, Prior systemic therapy, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take strong CYP3A4 inducers or inhibitors starting 14 days before and during the study.

Is larotrectinib safe for treating thyroid cancer?

Larotrectinib has been used safely in a patient with thyroid cancer, showing a complete response without reported safety issues. It is a targeted therapy that may offer a treatment option for those with specific genetic profiles in thyroid cancer. ^{1 2 3 4 5}

What makes the drug larotrectinib unique for treating thyroid cancer?

Larotrectinib is unique because it is a highly selective TRK inhibitor that can effectively treat thyroid cancer with specific genetic mutations (NTRK3 fusion-positive), especially when the cancer does not respond to standard radioactive iodine therapy. It has shown promising results, including complete responses in some patients, offering a new option for those with limited treatment choices. ^{2 4 6 7 8}

Research Team

Theodore W. Laetsch

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

This trial is for people of any age over 1 year with a specific type of thyroid cancer, who've had surgery and possibly other treatments for neck metastases. They must have certain lung nodules seen on CT scans and an NTRK gene fusion without resistance mutations. Good performance status and organ function are required, including specific blood cell counts and creatinine levels.

Inclusion Criteria

I am at least 1 year old.

I am 16 years old or older.

My organs are functioning well.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Larotrectinib Treatment

Participants receive larotrectinib monotherapy for 6 months at the FDA-approved dose

6 months

131I Therapy

Participants receive 131I therapy after 6 months of larotrectinib. Larotrectinib is continued for 5 days after RAI therapy

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Treatment Details

Interventions

• 131I therapy (Radiopharmaceutical)
• Larotrectinib (TRK Inhibitor)

Trial Overview The study tests Larotrectinib's ability to improve the effectiveness of radioactive iodine (RAI) therapy in treating advanced differentiated thyroid cancer after surgery. It aims to see if this drug can help those who don't fully respond to RAI, which has risks like pulmonary fibrosis and secondary cancers.

Participant Groups

Group I: Larotrectinib monotherapy with 131I therapy Experimental Treatment 2 Interventions

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.

131I therapy is already approved in Canada for the following indications:

Approved in Canada as Radioactive Iodine Therapy for:

• Thyroid cancer
• Hyperthyroidism

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

MD Anderson Cancer Center Houston, TX

Children's Hospital of Philadelphia Philadelphia, PA

Who Is Running the Clinical Trial?

Theodore Laetsch

Lead Sponsor

Trials

4

Patients Recruited

80+

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Patients Recruited

11,400,000+

Bayer

Industry Sponsor

Trials

2291

Patients Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multikinase inhibitors for the treatment of radioiodine refractory thyroid cancer: what have we learned from the 'real-world' experience? Costante, G.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete response to larotrectinib treatment in a patient with papillary thyroid cancer harboring an ETV6-NTRK3 gene fusion. Pitoia, F.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorafenib in radioactive iodine-refractory well-differentiated metastatic thyroid cancer. McFarland, DC., Misiukiewicz, KJ.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of multikinase inhibitors/lenvatinib in singular thyroid cancer scenarios. Zafón, C., Castelo, B.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of multi-kinase inhibitors in patients with radioiodine-refractory differentiated thyroid cancer: a systematic review and meta-analysis of clinical trials. Su, J., Wang, M., Fu, Y., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of multikinase inhibitors/lenvatinib concomitant with radioiodine for the treatment of radioiodine refractory differentiated thyroid cancer. Herranz, UA.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation. Schmidt, A., Iglesias, L., Klain, M., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib in Advanced, Radioactive Iodine-Refractory, Differentiated Thyroid Carcinoma. Yeung, KT., Cohen, EE.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Multikinase inhibitors for the treatment of radioiodine refractory thyroid cancer: what have we learned from the 'real-world' experience? [2021]

2. England pubmed.ncbi.nlm.nih.gov

Complete response to larotrectinib treatment in a patient with papillary thyroid cancer harboring an ETV6-NTRK3 gene fusion. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Sorafenib in radioactive iodine-refractory well-differentiated metastatic thyroid cancer. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Use of multikinase inhibitors/lenvatinib in singular thyroid cancer scenarios. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of multi-kinase inhibitors in patients with radioiodine-refractory differentiated thyroid cancer: a systematic review and meta-analysis of clinical trials. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Use of multikinase inhibitors/lenvatinib concomitant with radioiodine for the treatment of radioiodine refractory differentiated thyroid cancer. [2023]

7. Brazil pubmed.ncbi.nlm.nih.gov

Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Lenvatinib in Advanced, Radioactive Iodine-Refractory, Differentiated Thyroid Carcinoma. [2015]