Clinical Trials /

A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer

NCT04211337

Description:

The reason for this study is to see if the study drug selpercatinib is safe and more effective compared to a standard treatment in participants with rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC) that cannot be removed by surgery or has spread to other parts of the body. Participants who are assigned to the standard treatment and discontinue due to progressive disease have the option to potentially crossover to selpercatinib.

Related Conditions:
  • Thyroid Gland Medullary Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer
  • Official Title: A Multicenter, Randomized, Open-label, Phase 3 Trial Comparing Selpercatinib to Physicians Choice of Cabozantinib or Vandetanib in Patients With Progressive, Advanced, Kinase Inhibitor Naïve, RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531)

Clinical Trial IDs

  • ORG STUDY ID: 17478
  • SECONDARY ID: J2G-MC-JZJB
  • SECONDARY ID: 2019-001978-28
  • NCT ID: NCT04211337

Conditions

  • Medullary Thyroid Cancer

Interventions

DrugSynonymsArms
SelpercatinibLY3527723, LOXO-292Selpercatinib
CabozantinibCabozantinib or Vandetanib
VandetanibCabozantinib or Vandetanib

Purpose

The reason for this study is to see if the study drug selpercatinib is safe and more effective compared to a standard treatment in participants with rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC) that cannot be removed by surgery or has spread to other parts of the body. Participants who are assigned to the standard treatment and discontinue due to progressive disease have the option to potentially crossover to selpercatinib.

Trial Arms

NameTypeDescriptionInterventions
SelpercatinibExperimentalSelpercatinib given orally.
  • Selpercatinib
Cabozantinib or VandetanibActive ComparatorCabozantinib or vandetanib given orally.
  • Cabozantinib
  • Vandetanib

Eligibility Criteria

        -  At least 18 years of age (participants as young as 12 years of age will be allowed if
             permitted by local regulatory authorities).

          -  Histologically or cytologically confirmed, unresectable, locally advanced and/or
             metastatic MTC and no prior history of treatment with kinase inhibitors for
             advanced/metastatic disease.

          -  Radiographic progressive, measurable disease per Response Evaluation Criteria in Solid
             Tumors (RECIST) 1.1 at screening compared with a previous image taken within the prior
             14 months as assessed by central review.

          -  A defined/acceptable RET gene alteration identified in a tumor, germline
             deoxyribonucleic acid (DNA) or blood sample.

               -  Tumor tissue in sufficient quantity to allow for retrospective central analysis
                  of RET mutation status

          -  Eastern Cooperative Oncology Group performance status score of 0 to 2.

          -  Adequate hematologic, hepatic, and renal function and electrolytes.

          -  Men and 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.

          -  Ability to swallow capsules.

        Exclusion Criteria:

          -  An additional validated oncogenic driver in MTC if known that could cause resistance
             to selpercatinib treatment. Examples include, but are not limited to RAS or BRAF gene
             mutations and NTRK gene fusions.

          -  Symptomatic central nervous system (CNS) metastases, leptomeningeal carcinomatosis, or
             untreated spinal cord compression.

          -  Clinically significant active cardiovascular disease or history of myocardial
             infarction within 6 months, history of Torsades de pointes, or prolongation of the
             QTcF >470 milliseconds on more than one electrocardiogram (ECG) during screening.
             Participants who are intended to receive vandetanib if randomized to the control arm
             ineligible if QTcF is >450 milliseconds.

          -  Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing
             uncontrolled intercurrent illness.

          -  Active hemorrhage or at significant risk for hemorrhage.

          -  Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or
             malignancy diagnosed ≥2 years previously and not currently active. Participants with
             multiple endocrine neoplasia type 2 (MEN2) associated pheochromocytoma may be
             eligible.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR)
Time Frame:Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause (Estimated at up to 30 Months)
Safety Issue:
Description:TFFS by BICR

Secondary Outcome Measures

Measure:Progression Free Survival (PFS) by BICR
Time Frame:Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 30 Months)
Safety Issue:
Description:PFS by BICR
Measure:Overall Response Rate (ORR): Percentage of Participants with Complete Response (CR) or Partial Response (PR) by BICR
Time Frame:Baseline through Disease Progression or Death (Estimated at up to 30 Months)
Safety Issue:
Description:ORR: Percentage of Participants with CR or PR by BICR
Measure:Duration of Response (DoR) by BICR
Time Frame:Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Estimated at up to 30 Months)
Safety Issue:
Description:DoR by BICR
Measure:Overall Survival (OS)
Time Frame:Baseline to Date of Death from Any Cause (Estimated at up to 60 Months)
Safety Issue:
Description:OS
Measure:PFS2 by Investigator
Time Frame:Baseline to Second Disease Progression or Death from Any Cause (Estimated at up to 48 Months)
Safety Issue:
Description:PFS2 by Investigator
Measure:Comparative Tolerability: Patient-Reported Outcomes (Functional Assessment of Cancer Therapy-Side Effects [FACT-GP5])
Time Frame:Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause (30 months)
Safety Issue:
Description:Comparative Tolerability: Patient-Reported Outcomes (FACT-GP5)
Measure:The Concordance of the Local Lab and the Central Lab RET Results: Percentage of Participants with RET-Positive Specimens as Called by the Central Lab, which is also RET-Positive as Called by a Local Lab (Positive Percent Agreement)
Time Frame:Baseline
Safety Issue:
Description:The Concordance of the Local Lab and the Central Lab RET Results: Percentage of Participants with RET-Positive Specimens as Called by the Central Lab, which is also RET-Positive as Called by a Local Lab (Positive Percent Agreement)

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • medullary thyroid carcinoma
  • targeted therapy

Last Updated

January 6, 2021