Selpercatinib + I-131 for Thyroid Cancer
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Massachusetts General Hospital
Must not be taking: Investigational agents, QTc prolongation drugs
Disqualifiers: Symptomatic CNS metastasis, Cardiovascular disease, Uncontrolled hypertension, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This research is being done to determine the efficacy of selpercatinib to restore radioactive iodine (I-131 NaI) uptake and allow for I-131 treatment in people with RET fusion-positive radioiodine-refractory thyroid cancer.
This research study involves the study drug selpercatinib in combination with standard of care treatments, I-131 and thyrotropin alfa (rhTSH).
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking medications that cause QTc prolongation (a heart rhythm condition) or if you have had certain treatments like chemotherapy or radiotherapy within the last 4 weeks.
What data supports the effectiveness of the drug Selpercatinib for thyroid cancer?
Selpercatinib has been shown to be effective in treating advanced RET-altered thyroid cancer, with a high overall response rate in clinical trials. It was approved by the FDA based on significant responses in patients with RET fusion-positive thyroid cancer, demonstrating prolonged durations of response.
12345Is the combination of Selpercatinib and I-131 safe for humans?
Selpercatinib has been shown to have an acceptable safety profile in clinical trials for lung and thyroid cancers, with common side effects including high blood pressure and liver enzyme changes. Most side effects were manageable with dose adjustments, and only a few patients stopped treatment due to these effects. The product label warns about potential risks like liver damage, high blood pressure, heart rhythm changes, bleeding, allergic reactions, and risks to unborn babies.
13567What makes the drug Selpercatinib unique for thyroid cancer treatment?
Selpercatinib is unique because it specifically targets RET gene alterations, which are changes in a gene that can drive cancer growth. This drug is particularly effective for patients whose thyroid cancer is resistant to radioactive iodine, offering a new option for those with limited treatment choices.
12368Eligibility Criteria
Adults and children (12+) with certain types of advanced thyroid cancer that have a specific gene change called RET fusion. They must be able to swallow pills, not have had recent major treatments or surgeries, and should not be pregnant or breastfeeding. People with controlled HIV or hepatitis are eligible, but those with serious heart conditions, uncontrolled infections, or other severe illnesses cannot join.Inclusion Criteria
WOCBP must have a negative pregnancy test (serum or urine) within 24 hours prior to initiating study treatment, and not be breast-feeding during treatment and for ≥1 week after the last dose of study therapy
I am between 12 and 18 years old with a visible tumor.
Ability to understand and the willingness to sign a written informed consent document
+25 more
Exclusion Criteria
I have high or low calcium levels causing symptoms.
I do not have brain metastases causing symptoms or at risk of spinal cord compression.
I am taking medication that can affect my heart's rhythm.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive selpercatinib for 4 weeks, with a therapeutic dose of I-131 NaI administered in the fourth week. A second 4-week course may be offered if radioiodine uptake is restored.
4-8 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment, with follow-up visits for up to 2 years.
2 years
Participant Groups
The trial is testing if the drug selpercatinib can make thyroid cancers that no longer respond to radioactive iodine treatment start responding again. Participants will receive selpercatinib along with standard treatments including I-131 and rhTSH injections.
1Treatment groups
Experimental Treatment
Group I: SELPERCATINIB + I-131 NaIExperimental Treatment3 Interventions
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
* Participants will be treated with Selpercatinib for 4 weeks.
* In the fourth week of treatment, participants will receive a therapeutic dose of I-131 NaI.
* Those participants in whom radioiodine uptake has been restored may be offered a second 4-week course of selpercatinib plus I-131 NaI treatment
Selpercatinib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as RETEVMO for:
- RET fusion-positive or RET mutant thyroid cancers
- non-small cell lung cancer
- advanced or metastatic medullary thyroid cancer
- advanced or metastatic thyroid cancer with RET gene fusion
- locally advanced or metastatic solid tumors with RET gene fusion
🇪🇺 Approved in European Union as RETEVMO for:
- RET-driven non-small cell lung cancer
- medullary thyroid cancer
- thyroid cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
MedStar Washington Hospital CenterWashington, D.C., United States
Moffitt Cancer CenterTampa, FL
Children's Hospital of PhiladelphiaPhiladelphia, PA
MD Anderson Cancer CenterHouston, TX
More Trial Locations
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
Eli Lilly and CompanyIndustry Sponsor
References
Selpercatinib: First Approval. [2021]Selpercatinib (RETEVMO™) is a receptor tyrosine kinase RET (rearranged during transfection) inhibitor being developed by Loxo Oncology for the treatment of cancers harbouring RET alterations. Based on results from the phase I/II LIBRETTO-001 trial, selpercatinib was recently approved by the US FDA for the treatment of RET fusion-positive non-small-cell lung cancer, RET fusion-positive thyroid cancer and RET-mutant medullary thyroid cancer. This article summarizes the milestones in the development of selpercatinib leading to this first approval.
Efficacy and safety of selpercatinib in Chinese patients with advanced RET-altered thyroid cancers: results from the phase II LIBRETTO-321 study. [2022]Label="Background" NlmCategory="UNASSIGNED">Selpercatinib, a highly selective and potent REarranged during Transfection (RET) kinase inhibitor, is effective in advanced RET-altered thyroid cancer (TC). However, the efficacy and safety in Chinese patients are unknown.
FDA Approval Summary: Selpercatinib for the Treatment of Lung and Thyroid Cancers with RET Gene Mutations or Fusions. [2022]On May 8, 2020, the FDA granted accelerated approval to selpercatinib for (i) adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), (ii) adult and pediatric patients ≥12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy, and (iii) adult and pediatric patients ≥12 years of age with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine refractory (if radioactive iodine is appropriate). Approval was granted on the basis of the clinically important effects on the overall response rate (ORR) with prolonged duration of responses observed in a multicenter, open-label, multicohort clinical trial (LIBRETTO-001, NCT03157128) in patients whose tumors had RET alterations. ORRs within the approved patient populations ranged from 64% [95% confidence interval (CI), 54-73] in prior platinum-treated RET fusion-positive NSCLC to 100% (95% CI, 63-100) in systemic therapy-naïve RET fusion-positive thyroid cancer, with the majority of responders across indications demonstrating responses of at least 6 months. The product label includes warnings and precautions for hepatotoxicity, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, risk of impaired wound healing, and embryo-fetal toxicity. This is the first approval of a drug specifically for patients with RET alterations globally.
In search of a real "targeted" therapy for thyroid cancer. [2019]Over the past 5 years, patients with progressive radioactive iodine-refractory thyroid cancer have responded to "targeted" multikinase inhibitors, which inhibit angiogenesis and not the tumor cell. Here, selumetinib targets the mitogen-activated protein kinase pathway in papillary thyroid carcinoma and shows limited single-agent activity in the patients with tumors that harbor the (V600E)BRAF mutation.
Selpercatinib for lung and thyroid cancers with RET gene mutations or fusions. [2021]Aberrations in oncogene RET (rearranged during transfection) have been found to be the cause of different kinds of malignancies, especially in lung and thyroid cancers. Targeted therapy of RET-altered cancers using multi-kinase inhibitors (MKIs) has demonstrated limited clinical efficacy due to off-target toxicity. In May 2020, the U.S. Food and Drug Administration (FDA) approved a novel specific RET inhibitor for use in some subtypes of lung and thyroid cancers with RET alterations. In this review, we summarize the mechanism of action, pharmaceutical properties and clinical data of selpercatinib, and share some of our perspectives.
Selpercatinib: A Review in Advanced RET Fusion-Positive NSCLC. [2023]Selpercatinib (Retevmo®/Retsevmo®) is an orally-administered, selective inhibitor of rearranged during transfection (RET) kinase approved for the treatment of advanced RET fusion-positive non-small cell lung cancer (NSCLC). In a pivotal phase 1/2 clinical trial in this population, selpercatinib treatment was associated with robust and durable responses, including intracranial responses, in patients previously treated with platinum-based chemotherapy, as well as in treatment-naïve patients. Selpercatinib had a manageable tolerability profile and an acceptable safety profile; adverse events could generally be managed with dose reductions and only a small proportion of patients discontinued selpercatinib due to treatment-related adverse events. The most common treatment-related adverse events that were grade 3-4 in severity were hypertension, elevated alanine aminotransferase and elevated aspartate aminotransferase. Thus, currently available evidence suggests that selpercatinib is a promising new RET-targeted therapy option for patients with advanced RET fusion-positive NSCLC.
Selpercatinib-Induced Hypothyroidism Through Off-Target Inhibition of Type 2 Iodothyronine Deiodinase. [2023]The development of the selective RET inhibitors selpercatinib and pralsetinib has revolutionized the treatment of metastatic progressive RET-mutant medullary thyroid carcinoma (MTC) and other RET-driven cancers, given their more favorable side-effect profile. The aim of this study is to investigate the mechanisms of selpercatinib-induced thyroid dysfunction in athyreotic patients with RET-mutant MTC and in patients with RET-mutant non-small-cell lung cancer (NSCLC) who had a functional thyroid.
Sustained Response with Dose-reduced Selpercatinib in a Pediatric Patient with Metastatic NCOA4-RET Fusion Papillary Thyroid Carcinoma. [2023]Understanding the molecular landscape of papillary thyroid carcinoma (PTC), the most common thyroid cancer in children, creates additional therapeutic approaches. RET gene rearrangements are observed in pediatric PTC, and selective inhibition of RET is now possible with specific tyrosine kinase inhibitors designed to target diverse RET -activating alterations. We present a 13-year-old female with metastatic PTC, clinically resistant to radioactive iodine, and found to harbor a NCOA4-RET fusion. She responded to selpercatinib treatment with the elimination of supplemental oxygen need, marked reduction in pulmonary nodules and mediastinal lymphadenopathy, and biomarker decline. The response was maintained despite 2 dose reductions for possibly related weight gain.