Selpercatinib for Thyroid Cancer
(RAISE Trial)
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Children's Hospital of Philadelphia
Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors, QTc prolongers
Disqualifiers: Pregnancy, Cardiovascular disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
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 the trial and during the study. Also, you should avoid medications that cause QTc prolongation.
What data supports the effectiveness of the drug Selpercatinib for thyroid cancer?
Selpercatinib has been shown to be effective in treating advanced RET fusion-positive thyroid cancer, as demonstrated in the phase I/II LIBRETTO-001 trial, which led to its approval by the US FDA. It has also shown promising results in other RET fusion-positive cancers, indicating its potential as a targeted therapy.
12345Is selpercatinib safe for humans?
Selpercatinib has been shown to have an acceptable safety profile in clinical trials, with common side effects including high blood pressure, liver enzyme changes, and other manageable reactions. Serious warnings include potential liver damage, high blood pressure, heart rhythm changes, bleeding, allergic reactions, and risks to unborn babies.
23678What makes the drug Selpercatinib unique for treating thyroid cancer?
Selpercatinib is unique because it is a highly selective RET kinase inhibitor specifically targeting RET alterations, which are genetic changes found in some thyroid cancers. This drug is designed to be more precise in its action compared to other treatments, potentially leading to better outcomes for patients with RET fusion-positive thyroid cancer.
12345Eligibility Criteria
This trial is for young patients aged 2-21 with advanced differentiated thyroid cancer post-surgery, who have multiple lung nodules or enlarging ones consistent with metastatic disease. They must have a RET gene alteration and good organ function, including blood counts and liver/kidney performance.Inclusion Criteria
Agreement to use contraception during treatment
I am between 2 and 21 years old.
I can do most activities but need help with some.
+6 more
Exclusion Criteria
I have not had any systemic treatment for thyroid cancer.
I am not pregnant or breastfeeding.
I am not taking any strong drugs that affect liver enzyme activity.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Selpercatinib Treatment
Participants receive selpercatinib monotherapy for 6 months at the FDA-approved dose
6 months
131I Therapy
Participants receive 131I therapy after 6 months of selpercatinib treatment
5 days
Follow-up
Participants are monitored for safety and effectiveness after treatment
5 years
Participant Groups
The study tests Selpercatinib monotherapy before traditional radioactive iodine (RAI) therapy in pediatric thyroid cancer patients. It aims to see if pre-treatment with Selpercatinib can improve responses to RAI, which has limited effectiveness on its own.
1Treatment groups
Experimental Treatment
Group I: Experimental: Selpercatinib Monotherapy with 131I TherapyExperimental Treatment2 Interventions
Patients will receive selpercatinib monotherapy for 6 months at the FDA-approved dose.
Patients will receive 131I therapy after 6 months of selpercatinib. Selpercatinib 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 selpercatinib will proceed to 131I therapy and discontinue selpercatinib.
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:
Children's Hospital of PhiladelphiaPhiladelphia, PA
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Who Is Running the Clinical Trial?
Children's Hospital of PhiladelphiaLead Sponsor
United States Department of DefenseCollaborator
Eli Lilly and CompanyIndustry Sponsor
References
Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. [2022]Selpercatinib is a first-in-class, highly selective RET kinase inhibitor with CNS activity that has shown efficacy in RET fusion-positive lung and thyroid cancers. RET fusions occur rarely in other tumour types. We aimed to investigate the efficacy and safety of selpercatinib in a diverse group of patients with RET fusion-positive non-lung or thyroid advanced solid tumours (ie, a tumour-agnostic population).
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.
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.
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.
Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. [2023]Label="BACKGROUND" NlmCategory="BACKGROUND">Selpercatinib, a highly selective, potent RET inhibitor, has shown efficacy in advanced RET-mutant medullary thyroid cancer in a phase 1-2 trial, but its efficacy as compared with approved multikinase inhibitors is unclear.
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.
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.
FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors. [2023]On September 21, 2022, the FDA granted accelerated approval to selpercatinib (Retevmo, Eli Lilly and Company) for the treatment of adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. The approval was based on data from Study LOXO-RET-17001 (LIBRETTO-001; NCT03157128), an international, non-randomized, multi-cohort clinical trial that included patients with advanced solid tumors harboring RET alterations. The overall response rate in 41 patients with locally advanced or metastatic RET fusion-positive solid tumors other than non-small cell lung cancer (NSCLC) or thyroid cancer was 44% [95% confidence interval (CI), 28%-60%], with median duration of response 24.5 months (95% CI, 9.2-not evaluable). Patients with 10 of 14 tumor types with a variety of fusion partners had objective responses, including patients with the following tumors: pancreatic adenocarcinoma, colorectal, salivary, unknown primary, breast, soft-tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma. The recommendation for approval was supported by results from LIBRETTO-001 in patients with RET fusion-positive NSCLC and thyroid cancer, which formed the basis of prior approvals in these tumor types. The most common adverse reactions (>25%) were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. This is the first tissue-agnostic approval of a RET-directed targeted therapy.