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

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ClinicalTrials.gov Identifier: NCT04211337
Recruitment Status : Recruiting
First Posted : December 26, 2019
Last Update Posted : April 8, 2021
Sponsor:
Collaborator:
Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company

Study Description
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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.

Condition or disease Intervention/treatment Phase
Medullary Thyroid Cancer Drug: Selpercatinib Drug: Cabozantinib Drug: Vandetanib Phase 3

Expanded Access : An investigational treatment associated with this study is temporarily not available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 11, 2020
Estimated Primary Completion Date : May 20, 2024
Estimated Study Completion Date : November 13, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Selpercatinib
Selpercatinib given orally.
 Drug: Selpercatinib
Administered orally
Other Names:
  • LY3527723
  • LOXO-292
Active Comparator: Cabozantinib or Vandetanib
Cabozantinib or vandetanib given orally.
 Drug: Cabozantinib
Administered orally

Drug: Vandetanib
Administered orally


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. Overall Survival (OS) [ Time Frame: Baseline to Date of Death from Any Cause (Estimated at up to 60 Months) ]
    OS

  5. PFS2 by Investigator [ Time Frame: Baseline to Second Disease Progression or Death from Any Cause (Estimated at up to 48 Months) ]
    PFS2 by Investigator

  6. Comparative Tolerability: Percentage of Time with High Side Effect Bother Based on the Functional Assessment of Cancer Therapy-Side Effects (FACT-GP5) [ Time Frame: Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause (30 months) ]
    FACT-G is a validated instrument used to measure quality of life (QOL) in participants with cancer. The single FACT-G item, GP5, "I am bothered by side effects of treatment," is a summary measure of the overall impact of treatment toxicity, based upon its association with the number and degree of adverse events in clinical trials. It uses a 5-point rating scale (0="not at all" and 4=equals "very much"). Higher GP5 scores indicates more bother from side effects

  7. 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)


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 the BICR. Participants with measurable or non-measurable but evaluable disease are eligible; however, participants with non-measurable disease may not have disease limited to bone sites only.

  • 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 4 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 or malignancy diagnosed ≥2 years previously and not currently active. Participants with multiple endocrine neoplasia type 2 (MEN2) associated pheochromocytoma may be eligible.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04211337


Contacts
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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

Locations
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Sponsors and Collaborators
Eli Lilly and Company
Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company
Investigators
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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
More Information
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Additional Information:

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT04211337    
Other Study ID Numbers: 17478
J2G-MC-JZJB ( Other Identifier: Eli Lilly and Company )
2019-001978-28 ( EudraCT Number )
First Posted: December 26, 2019    Key Record Dates
Last Update Posted: April 8, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
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/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Lilly and Company:
medullary thyroid carcinoma
targeted therapy
Additional relevant MeSH terms:
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Thyroid Neoplasms
Carcinoma, Neuroendocrine
Thyroid Diseases
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
 Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue