Clinical Trial 22464

• Overview

  Study Title:

  Restoration of Radioiodine Uptake with Selpercatinib in RET Fusion-Positive Radioiodine-Refractory Thyroid Cancer: A Phase 2 Study Performed in Collaboration with the International Thyroid Oncology Group (ITOG)

  Summary:

  This research is being done to determine the efficacy of selpercatinib to restore radioactive iodine (I-131) uptake and allow for I-131 treatment in people with RET fusion-positive radioiodine-refractory thyroid cancer.

  Objective:

  Primary Objective: * Efficacy of selpercatinib to restore I-131 uptake and allow for I-131 treatment in participants with RAI-refractory RET fusion-positive thyroid cancer will be estimated. Objective response rate (ORR) per modified RECIST v1.1 at 6 months in enrolled participants will be determined as the primary endpoint in this open-label multicenter phase 2 study. * Response will be assessed by the Investigator by CT scans (or MRIs) of the neck and chest (and abdomen and pelvis in participants with documented metastasis in the abdomen and pelvis at screening), and physical examination, when applicable. Secondary Objectives: * The rate of restoration of I-131 uptake by pretreatment with selpercatinib will be estimated by whole body scan following I-131 treatment in patients with RET fusionpositive RAI-refractory thyroid cancer. * Thyroglobulin biochemical response rates in patients enrolled will be estimated. * Progression-free survival (PFS) and Overall Survival (OS). * Time to initiation of next systemic therapy will be estimated. * 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. * The structural, biochemical and complete response rate to selpercatinib plus I-131 treatment in adolescent patients 12 to <18 years of age without measurable disease at baseline will be reported in descriptive fashion.>

• Treatments

  Therapies:

  Radiotherapy; Therapy (NOS)

  Medications:

  Selpercatinib (); Thyrogen (); iodine-131 ()

• Inclusion Criteria

  Inclusion Criteria:
  • 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 must be 18 years of age or older and must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 that has progressed within 18 months of enrollment.
  • Participants should have no single tumor deposit exceeding 4.0 cm in the greatest dimension.
  • Participants must have RAI-refractory disease.
  • Participants may have received no more than a total cumulative RAI dose for treatment (not including RAI given for diagnostic purposes only) of 500 mCi (18.5 GBq).
  • Participants must have asymptomatic or minimally symptomatic disease, as judged by the treating investigator.
  • Prior external beam radiotherapy is allowed. For participants with disease limited to a prior radiotherapy field, this must be considered measurable per RECIST v1.1.
  • Participants may have had no more than one prior systemic therapy for RAI-refractory thyroid cancer, including lenvatinib, sorafenib, or other MKIs.
  • At least 28 days must have passed since any prior radiation or major surgery. At least 28 days must have passed since any prior systemic therapy for thyroid cancer, excluding thyroid hormone replacement.
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less.
  • Participants must have a life expectancy greater than 12 months.
  • Participants must have the ability to swallow medications and have no gastrointestinal abnormality that may alter medication absorption.
  • Participants must have adequate organ and marrow function.
  • Known human immunodeficiency virus (HIV)-infected participants on effective anti- retroviral therapy with an undetectable viral load within 6 months are eligible for this trial.
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Participants with treated brain metastases are eligible if the patient is asymptomatic AND follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
  • Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Participants with known history or current symptoms of cardiac disease or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
  • Women of child-bearing potential (WOCBP) and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 6 months after the last dose of study drug.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Other criteria may apply.

• Exclusion Criteria

  Exclusion Criteria:
  • Participants who have had chemotherapy, MKI or radiotherapy within 4 weeks.
  • Participants who have had I-131 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.
  • Participants with symptomatic CNS metastasis or lesions threatening for spinal cord compression and not eligible.
  • Participants with clinically significant active cardiovascular disease or history of Torsades de pointes, or prolongation of the corrected QT interval by Fridericia's formula (QTcF) >470 msec on more than one ECG during Screening. Correction of suspected drug-induced QTcF prolongation may be attempted at the investigator's discretion if clinically safe to do so.
  • Participants with uncontrolled hypertension at screening, as defined by >160/95 mm Hg.
  • Participants with uncontrolled hypertension at screening may be re-screened after appropriate medical therapy for hypertension.
  • Participants with an active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment, a clinical diagnosis or symptoms of interstitial lung disease, or other serious medical conditions which in the medical judgment of the investigator would prevent the patient from safely participating (screening for chronic conditions is not required).
  • Participants with uncontrolled symptomatic hyperthyroidism or hypothyroidism.
  • Participants with symptomatic hypercalcemia or hypocalcemia.
  • Participants with active hemorrhage or at significant risk for hemorrhage.
  • Participants who are taking a concomitant medication that is known to cause QTc prolongation ).
  • Participants with other uncontrolled serous intercurrent illness that would interfere with the ability to proceed with study therapy.

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