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.
Is the drug Larotrectinib a promising treatment for thyroid cancer?Yes, Larotrectinib is a promising drug for thyroid cancer, especially for patients whose cancer does not respond to radioactive iodine therapy. It has shown the ability to completely stop the cancer's growth in some cases, providing new hope for patients with limited treatment options.23578
What safety data exists for Larotrectinib in thyroid cancer treatment?The safety data for Larotrectinib in thyroid cancer treatment is limited but promising. A case study reported a complete response in a patient with papillary thyroid cancer harboring an ETV6-NTRK3 gene fusion, with sustained results for 11 months and complete intracranial responses in metastatic brain lesions after 7 months of treatment. This suggests Larotrectinib may be a viable option for patients with RAI-refractory differentiated thyroid cancer, although more extensive safety data is needed.14567
What data supports the idea that Larotrectinib for Thyroid Cancer is an effective drug?The available research does not provide specific data on Larotrectinib for Thyroid Cancer. Instead, it focuses on other treatments like multikinase inhibitors, such as sorafenib and lenvatinib, for radioiodine-refractory thyroid cancer. These drugs have shown improved outcomes in patients who do not respond to traditional radioactive iodine therapy. For example, lenvatinib has been shown to significantly improve the time patients live without the disease getting worse, compared to a placebo. However, there is no direct mention of Larotrectinib's effectiveness for thyroid cancer in the provided information.23467
Do I need to stop my current medications to join the trial?The trial does not specify if you need to stop all current medications, but you cannot take strong CYP3A4 inducers or inhibitors. These should be avoided 14 days before starting and during the study.
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.Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: Larotrectinib monotherapy with 131I therapyExperimental Treatment2 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 United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Radioactive Iodine Therapy for:
- Thyroid cancer
- Hyperthyroidism
🇪🇺 Approved in European Union as Radioactive Iodine Therapy for:
- Thyroid cancer
- Hyperthyroidism
🇨🇦 Approved in Canada as Radioactive Iodine Therapy for:
- Thyroid cancer
- Hyperthyroidism
Find a clinic near you
Research locations nearbySelect from list below to view details:
MD Anderson Cancer CenterHouston, TX
Children's Hospital of PhiladelphiaPhiladelphia, PA
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Who is running the clinical trial?
Theodore LaetschLead Sponsor
Children's Hospital of PhiladelphiaLead Sponsor
BayerIndustry Sponsor
References
Sorafenib in radioactive iodine-refractory well-differentiated metastatic thyroid cancer. [2021]Recent Phase III data presented at the American Society of Clinical Oncology (ASCO) 2013 annual conference by Brose et al led to the US Food and Drug Administration (FDA) approval of sorafenib for the treatment of well-differentiated radioactive iodine-resistant metastatic thyroid cancer. This is the second drug in 40 years to be FDA approved for this indication. Recent reviews and a meta-analysis reveal a modest ability to induce a partial remission but substantial ability to halt disease progression. Given the significant activating mutations present in thyroid cancer, many of which are inhibited by sorafenib, the next logical approach may be to combine targeted rational therapies if permitted by collective toxicity profiles. This systematic review aims to summarize the recent Phase II/III data leading to the FDA approval of sorafenib for radioactive iodine therapy differentiated thyroid cancer and highlights recent novel combination therapy trials.
Lenvatinib in Advanced, Radioactive Iodine-Refractory, Differentiated Thyroid Carcinoma. [2015]Management options are limited for patients with radioactive iodine refractory, locally advanced, or metastatic differentiated thyroid carcinoma. Prior to 2015, sorafenib, a multitargeted tyrosine kinase inhibitor, was the only approved treatment and was associated with a median progression-free survival (PFS) of 11 months and overall response rate (ORR) of 12% in a phase III trial. Lenvatinib, a multikinase inhibitor with high potency against VEGFR and FGFR demonstrated encouraging results in phase II trials. Recently, the pivotal SELECT trial provided the basis for the FDA approval of lenvatinib as a second targeted therapy for these patients. Median PFS of 18.3 months in the lenvatinib group was significantly improved from 3.6 months in the placebo group, with an HR of 0.21 (95% confidence interval, 0.4-0.31; P
Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation. [2023]Radioiodine (RAI)-refractory thyroid cancer is an uncommon entity, occurring with an estimated incidence of 4-5 cases/year/million people. RAI refractoriness is more frequent in older patients, in those with large metastases, in poorly differentiated thyroid cancer, and in those tumors with high 18-fluordeoxyglucose uptake on PET/CT. These patients have a 10-year survival rate of less than 10%. In recent years, new therapeutic agents with molecular targets have become available, with multikinase inhibitors (MKIs) being the most investigated drugs. Two of these compounds, sorafenib and lenvatinib, have shown significant objective response rates and have significantly improved the progression-free survival in the two largest published prospective trials on MKI use. However, no overall survival benefit has been achieved yet. This is probably related to the crossover that occurs in most patients who progress on placebo treatment to the open treatment of these studies. In consequence, the challenge is to correctly identify which patients will benefit from these treatments. It is also crucial to understand the appropriate timing to initiate MKI treatment and when to stop it. The purpose of this article is to define RAI refractoriness, to summarize which therapies are available for this condition, and to review how to select patients who are suitable for them.
Multikinase inhibitors for the treatment of radioiodine refractory thyroid cancer: what have we learned from the 'real-world' experience? [2021]Several molecularly targeted drugs for treating radioiodine resistant differentiated thyroid carcinomas (RAIR-DTC) have been identified. Among these, sorafenib and lenvatinib have been approved for clinical use in many countries. The present review will analyze efficacy and safety 'real-world' data (RWD) emerging after their commercialization.
Complete response to larotrectinib treatment in a patient with papillary thyroid cancer harboring an ETV6-NTRK3 gene fusion. [2023]Larotrectinib, a highly selective TRK inhibitor, was administered to a patient with rapidly progressing radioactive iodine-refractory papillary NTRK3 fusion-positive thyroid cancer. The patient achieved a durable (sustained for 11 months) complete response after 2 months of treatment and complete intracranial responses in metastatic brain lesions after 7 months of treatment. Larotrectinib may provide a therapeutic route for patients with RAI-R-differentiated thyroid cancer who might otherwise have few treatment options.
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]Radioiodine-refractory differentiated thyroid cancer (RAI-rDTC) has frequently been associated with poor prognosis. We conducted a meta-analysis of published randomized controlled trials to evaluate multi-kinase inhibitors' efficacy and safety profile treatment.
Use of multikinase inhibitors/lenvatinib in singular thyroid cancer scenarios. [2022]Thyroid cancer is the most frequent endocrine tumor. In locally advanced or metastatic disease there are only two types of treatment available: radioactive iodine (RAI) while the disease is RAI-sensitive and multikinase inhibitors, lenvatinib and sorafenib, when the disease becomes RAI-refractory. The objective of this publication is to review the current knowledge on the use of targeted therapy and the specific practical considerations concerning lenvatinib in the treatment of patients with differentiated thyroid cancer under special circumstances.
Use of multikinase inhibitors/lenvatinib concomitant with radioiodine for the treatment of radioiodine refractory differentiated thyroid cancer. [2023]Thyroid cancer is the most frequent endocrine tumor. However, in locally advanced or metastatic disease we have only two types of treatment at our disposal: radioactive iodine (RAI) when the disease is RAI-sensitive and multikinase inhibitors (MKIs), lenvatinib and sorafenib, when the disease becomes RAI-refractory (RR). This review revisits the published data on the potential combination of MKIs/lenvatinib with RAI in RR-differentiated thyroid cancer and evaluates some special situations where this combination may be of particular interest. The combination of MKIs/lenvatinib with RAI could, at least hypothetically, improve the efficacy seen in both treatments alone via a synergistic effect and with a lower rate of toxicity rates. Early preclinical data support this notion, while its generalized use awaits the results of ongoing clinical trials.