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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 : February 18, 2020
Sponsor:
Collaborator:
Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company

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 available outside the clinical trial.   More info ...

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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 10, 2020
Estimated Primary Completion Date : February 17, 2023
Estimated Study Completion Date : December 27, 2024


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




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: 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)

  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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 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.

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
Show Show 124 study locations
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

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: February 18, 2020
Last Verified: February 2020
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
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Thyroid Diseases
Endocrine System Diseases
Adenocarcinoma
Carcinoma