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).
Participants must have histologically- or cytologically-confirmed follicular-derived nonanaplastic thyroid cancer that is metastatic and/or unresectable AND harbors a known oncogenic RET gene fusion, performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalently accredited diagnostic laboratory.
Tumor tissue or liquid biopsy-based next-generation sequencing (NGS), quantitative polymerase chain reaction (qPCR), and fluorescence in situ hybridization (FISH) for RET gene fusion detection will be permitted.
Participants ≥ 18 years of age must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Participants should have no single tumor deposit exceeding 4.0 cm in the greatest dimension.
Participants who have had chemotherapy, MKI or radiotherapy within 4 weeks.
Participants who have had I-131 NaI treatment within 12 months.
Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia.
Participants who are receiving any other investigational agents.
Single group
Selpercatinib
DrugSelpercatinib Oral, twice daily during initial treatment period (28 Days). A second course of selpercatinib if the participant is demonstrating clinical benefit to the initial course selpercatinib and deemed clinically appropriate by the treating investigator
Sodium Iodine I-131
DrugI-131 NaI, oral, is a standard treatment for all types of follicular-derived thyroid cancers, except anaplastic thyroid cancer
rhTSH
DrugRhTSH injection, dosage per protocol, timing per protocol during the initial treatment period per standard of care. Participants may receive a second course of rhTSH if the participant is demonstrating clinical benefit to the initial course rhTSH and deemed clinically appropriate by the treating investigator.
Objective Response Rate
RECIST v1.1 or Nies criteria in adolescents without RECIST-measurable disease The primary endpoint is best overall response (ORR) (CR and PR) at 6 months. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).Complete Response (CR) Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters
Number of Participants with Treatment Related Adverse Events as Assessed CTCAE v5.0
The safety profile of selpercatinib plus I-131 treatment in this patient population, will be evaluated by assessing by the incidence of treatment-related adverse events per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Rate of restoration of I-131 uptake
The estimated rate of restoration of I-131 uptake in patients with RAI-refractory RET fusion-positive thyroid cancer treated with selpercatinib will be estimated by determining the rate of positive whole body scans performed after I-131 administration.
thyroglobulin biochemical response rate
The estimated best thyroglobulin biochemical response rates will be determined by comparing serial serum thyroglobulin levels taken every 3 months following treatment to that of the pretreatment baseline level in participants with measurable serum thyroglobulin. Best biochemical response is defined as follows: equals normalization of thyroglobulin level; partial response equals ≥50% decrease from baseline thyroglobulin; stable disease equals \<50% decrease or increase from baseline; and biochemical progression equals ≥50% increase from baseline (each maintained for at least 4 weeks).
Progression Free Survival
Kaplan-Meier Method
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Massachusetts General Hospital
Lead sponsor
Eli Lilly and Company
Collaborator
