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.

Related Conditions:
  • Thyroid Gland Medullary Carcinoma
Recruiting Status:

Not yet 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.

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 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 gene
             mutations and ALK 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:Not yet recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • medullary thyroid carcinoma
  • targeted therapy

Last Updated

December 24, 2019