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A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04211337
Recruitment Status : Recruiting
First Posted : December 26, 2019
Last Update Posted : October 19, 2020
Sponsor:
Collaborator:
Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE December 24, 2019
First Posted Date  ICMJE December 26, 2019
Last Update Posted Date October 19, 2020
Actual Study Start Date  ICMJE February 11, 2020
Estimated Primary Completion Date May 20, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 24, 2019)
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) ]
TFFS by BICR
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 24, 2019)
  • Progression Free Survival (PFS) by BICR [ Time Frame: Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 30 Months) ]
    PFS by BICR
  • 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) ]
    ORR: Percentage of Participants with CR or PR by BICR
  • 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) ]
    DoR by BICR
  • Overall Survival (OS) [ Time Frame: Baseline to Date of Death from Any Cause (Estimated at up to 60 Months) ]
    OS
  • PFS2 by Investigator [ Time Frame: Baseline to Second Disease Progression or Death from Any Cause (Estimated at up to 48 Months) ]
    PFS2 by Investigator
  • 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) ]
    Comparative Tolerability: Patient-Reported Outcomes (FACT-GP5)
  • 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 ]
    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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer
Official Title  ICMJE 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)
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Medullary Thyroid Cancer
Intervention  ICMJE
  • Drug: Selpercatinib
    Administered orally
    Other Names:
    • LY3527723
    • LOXO-292
  • Drug: Cabozantinib
    Administered orally
  • Drug: Vandetanib
    Administered orally
Study Arms  ICMJE
  • Experimental: Selpercatinib
    Selpercatinib given orally.
    Intervention: Drug: Selpercatinib
  • Active Comparator: Cabozantinib or Vandetanib
    Cabozantinib or vandetanib given orally.
    Interventions:
    • Drug: Cabozantinib
    • Drug: Vandetanib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 24, 2019)
400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 13, 2026
Estimated Primary Completion Date May 20, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: There will be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 ClinicalTrials.gov@lilly.com
Listed Location Countries  ICMJE Australia,   Belgium,   Brazil,   Canada,   China,   Czechia,   France,   Germany,   Greece,   India,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Russian Federation,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04211337
Other Study ID Numbers  ICMJE 17478
J2G-MC-JZJB ( Other Identifier: Eli Lilly and Company )
2019-001978-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: http://vivli.org/
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company
Investigators  ICMJE
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP