Selpercatinib Pre-RAI in Patients With RET Fusion Thyroid Cancer (RAISE)

Launched by CHILDREN'S HOSPITAL OF PHILADELPHIA · Jun 10, 2024

Keywords

ClinConnect Summary

The RAISE clinical trial is studying a medication called selpercatinib for children and young adults with a specific type of thyroid cancer known as differentiated thyroid cancer, particularly papillary thyroid cancer. Traditionally, patients with advanced thyroid cancer receive radioactive iodine therapy after surgery, but this treatment doesn’t work well for everyone and can cause serious side effects. This trial aims to see if selpercatinib can provide a better option for patients who have certain genetic changes in their cancer, known as RET gene alterations.

To participate, patients need to be between 2 and 21 years old, have had surgery for their thyroid cancer, and have evidence of cancer spread to the lungs. They must also have specific tests confirming the RET gene alteration. Participants can expect to receive the study drug selpercatinib and will be closely monitored throughout the trial. It’s important for potential participants to discuss any medications they are taking with their doctor and to use effective birth control if they are of childbearing age, as selpercatinib may affect fertility. This trial is currently recruiting participants, providing a hopeful opportunity for those affected by this challenging condition.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age 2-21 years, inclusive
• • 2. Histologic diagnosis of a differentiated thyroid cancer, status post 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 (Computed Tomography) 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 activating RET gene alteration (fusion or mutation). The RET alteration result should be generated from a laboratory with specific certifications (depending on country requirement) that clearly denotes the presence of a RET alteration 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) ≥1500/µL
• • Platelet count ≥ 100,000/µL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• • Hemoglobin ≥ 9.0 g/dL at baseline (may receive Red Blood Cell 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.
• • C. Adequate Liver Function
• • Bilirubin (sum of conjugated + unconjugated) \< / = 1.5 x upper limit of normal (ULN) for age. Except participants with a documented history of Gilbert syndrome who must have a total bilirubin level of \<3.0X ULN
• • Alanine aminotransferase (ALT) \<2.5X ULN OR \<5x ULN if the liver has tumor involvement. For the purpose of this study, the ULN for ALT is 45 U/L.
• • Serum albumin ≥ 2 g/dL
• • 7. Patient must have normal serum potassium, calcium, and magnesium levels (may be receiving supplements)
• • 8. Men with partners of childbearing potential or women of childbearing potential must agree to use a highly effective contraceptive method during treatment with study drug and for 6 months following the last dose of study drug. Selpercatinib could impair fertility in males and females. Advise women not to breastfeed during treatment with selpercatinib and for 1 week following the final dose
• • 9. Women of childbearing potential must have a negative pregnancy test (serum or urine, consistent with local regulations) documented within 24 hours prior to treatment with study drug and at least monthly while on study treatment
• Exclusion Criteria:
• • 1. No prior systemic therapy for thyroid cancer, including RET inhibitors or 131I.
• • 2. Females who are pregnant or breastfeeding are excluded due to the potential risks of selpercatinib and radioactive iodine 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.
• • 4. Patients with clinically significant active cardiovascular disease, Torsades de pointes, or history of myocardial infarction within 6 months prior to planned start of study treatment or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) \>470 msec.
• • 5. Have clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the drug.
• • 6. Are taking a concomitant medication that is known to cause QTc prolongation.
• • 7. Active hemorrhage or at significant risk for hemorrhage.
• • 8. Uncontrolled hypertension (blood pressure greater than 140/90 in adults or greater than the 95% for height and gender in children). Use of anti-hypertensives to control blood pressure is permitted.