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

Sponsor
Loxo Oncology, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04211337
Collaborator
Eli Lilly and Company (Industry)
400
Enrollment
154
Locations
2
Arms
81.1
Anticipated Duration (Months)
2.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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
Phase 3

Detailed Description

Adaptive sample size re-estimation will be performed at interim analysis. The sample size could be increased from approximately 250 to 400 depending on the results of interim analysis.

Study Design

Study Type:
Interventional
Anticipated 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 :
Feb 11, 2020
Anticipated Primary Completion Date :
May 20, 2024
Anticipated Study Completion Date :
Nov 13, 2026

Arms and Interventions

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

    Primary Outcome Measures

    1. Progression Free Survival (PFS) by BICR [Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 30 Months)]

      PFS by BICR

    Secondary Outcome Measures

    1. Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR) [Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause (Estimated at up to 30 Months)]

      TFFS by BICR

    2. Overall Response Rate (ORR): Percentage of Participants with Complete Response (CR) or Partial Response (PR) by BICR [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 [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) [Baseline to Date of Death from Any Cause (Estimated at up to 60 Months)]

      OS

    5. PFS2 by Investigator [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) [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) [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

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    • 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 are 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

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35233
    2 Mayo Clinic Hospital Phoenix Arizona United States 85054
    3 City of Hope National Medical Center Duarte California United States 91010-0269
    4 UCLA Medical Center Los Angeles California United States 90095
    5 University of California, Davis - Health Systems Sacramento California United States 95817
    6 UCSF Medical Center at Mission Bay San Francisco California United States 94158
    7 Los Angeles Biomedical Research Institute at Harbor - UCLA Medical Torrance California United States 90502
    8 Mayo Clinic in Florida Jacksonville Florida United States 32224
    9 Emory University Atlanta Georgia United States 30322
    10 University of Chi Med Center Chicago Illinois United States 60637
    11 Massachusetts General Hospital Boston Massachusetts United States 02114
    12 University of Michigan Ann Arbor Michigan United States 48109
    13 Memorial Sloan Kettering Cancer Center New York New York United States 10017
    14 University of Cincinnati Cancer Institute Cincinnati Ohio United States 45267
    15 Ohio State University Medical Center Columbus Ohio United States 43210
    16 University of Pennsylvania Hospital Philadelphia Pennsylvania United States 19104
    17 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
    18 University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    19 University of Wisconsin-Madison Hospital and Health Clinic Madison Wisconsin United States 53792-4108
    20 Chris O'Brien Lifehouse Camperdown New South Wales Australia 2050
    21 Royal North Shore Hospital St. Leonards New South Wales Australia 2065
    22 Peter MacCallum Cancer Centre Melbourne Victoria Australia 3000
    23 The Alfred Hospital Melbourne Victoria Australia 3004
    24 Sir Charles Gairdner Hospital Nedlands Western Australia Australia 6009
    25 Universitair Ziekenhuis Antwerpen Edegem Belgium 2650
    26 Centre Hospitalier Universitaire Sart Tilman Liege Belgium 4000
    27 Oncocentro BH Belo Horizonte Minas Gerais Brazil 30260-680
    28 Hospital de Cancer de Londrina Londrina Paraná Brazil 86015-520
    29 Hospital de Clinicas de Porto Alegre Porto Alegre Rio Grande Do Sul Brazil 90035-003
    30 Instituto de Educação, Pesquisa e Gestão em Saúde Rio de Janeiro RJ Brazil 22793-080
    31 Fundação Pio XII - Hospital de Câncer de Barretos Barretos Sao Paulo Brazil 14784-400
    32 Clinica Onco Star Sao Paulo SP Brazil 04501-000
    33 Hospital PUC-CAMPINAS Campinas São Paulo Brazil 13060-904
    34 Hospital das Clinicas da FMRP Ribeirão Preto São Paulo Brazil 14051-140
    35 INCA Hospital do Câncer III Rio de Janeiro Brazil 20560-120
    36 Oncoclinicas Rio de Janeiro S.A. Rio de Janeiro Brazil 22250-905
    37 Soc. Beneficente de Senhoras Hospital Sirio Libanes-Oncology Sao Paolo Brazil 01308-050
    38 Icesp - Instituto Do Câncer Do Estado de São Paulo Sao Paulo Brazil 01246000
    39 Centro Paulista de Oncologia São Paulo Brazil 04538-133
    40 London Health Science Centre - Victoria Hospital London Ontario Canada N6A 5W9
    41 Princess Margaret Hospital Toronto Ontario Canada M5G 2M9
    42 Anhui Provincial Hospital Hefei Anhui China 230001
    43 Beijing Tongren Hospital affiliated to Capital Medical Unive Beijing Beijing China 100730
    44 The First Affiliated Hospital of Fujian Medical University Fujian Fuzhou China 350005
    45 Gansu Province Cancer Hospital Lanzhou Gansu China 730050
    46 Sun Yat-sen University Cancer Center Guangzhou Guangdong China 510060
    47 Harbin Medical University Cancer Hospital Harbin Heilongjiang China 150081
    48 Henan Cancer Hospital Zhengzhou Henan China 450008
    49 Hunan Cancer Hospital Changsha Hunan China 410013
    50 Jilin Cancer Hospital Chang Chun Ji Lin China 130012
    51 Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing Jiangsu China 210000
    52 Jinan Central Hospital Jinan Shandong China 250013
    53 Fudan University Shanghai Cancer Center Shanghai Shanghai China 200032
    54 West China Hospital of Sichuan University Cheng Du Sichuan China 610041
    55 First Affiliated Hospital of Kunming Medical University Kunming Yunnan China 650032
    56 Zhejiang Provincial People's Hospital Hangzhou Zhejiang China 310014
    57 Sir Run Run Shaw Hospital Hangzhou Zhejiang China 310016
    58 Zhejiang Cancer Hospital Hangzhou Zhejiang China 310022
    59 Chongqing Cancer Hospital Chongqing China 400030
    60 Tianjin Medical University Cancer Institute and Hospital Tianjin China 300060
    61 Fakultni nemocnice Brno Brno Czechia 62500
    62 Fakultni nemocnice Olomouc Olomouc Czechia 779 00
    63 Fakultni Nemocnice v Motole Praha 5 Czechia 150 06
    64 Assistance Publique Hôpitaux de Marseille - Hôpital Nord Marseille Bouches-du-Rhône France 13915
    65 Centre Georges François Leclerc Dijon Côte-d'Or France 21079
    66 Centre Hospitalier Universitaire d'Angers Angers Maine-et-Loire France 49933
    67 Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne Clermont-Ferrand Puy-de-Dôme France 63011
    68 Centre Leon Berard Lyon Rhône-Alpes France 69008
    69 Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest Bordeaux France 33076
    70 Centre François Baclesse Caen Cedex 5 France 14076
    71 Hôpital C. HURIEZ Lille France 59037
    72 Hopital Pitie Salpetriere -Unité Thyroïde-Tumeurs Endocrines PARIS- cedex 13 France 765651
    73 Institut de cancérologie Strasbourg Europe Strasbourg France 67386
    74 Institut Claudius Regaud Toulouse cedex 9 France 31059
    75 Gustave Roussy Villejuif Cedex France 94805
    76 Klinikum der Universität München Großhadern München Bayern Germany 81377
    77 Universitätsklinikum Würzburg A. ö. R. Würzburg Bayern Germany 97080
    78 Medizinische Hochschule Hanover Hannover Niedersachsen Germany 30625
    79 Universitätsmedizin Johannes Gutenberg Universität Mainz Mainz Rheinland-Pfalz Germany 55131
    80 Charité Campus Mitte Berlin Germany 10117
    81 Universitaetsklinikum Essen Essen Germany 45147
    82 Studiengesellschaft Hämato-Onkologie Hamburg - Prof Laack & Partner Hamburg Germany 20251
    83 Otto-von-Guericke-Universität Magdeburg Germany 39120
    84 Alexandra General Hospital of Athens Athens Attikí Greece 11528
    85 University General Hospital of Heraklion Heraklion Irakleío Greece 711 10
    86 European Interbalkan Medical Center Thessaloniki Thessaloníki Greece 570 01
    87 Regional Cancer Centre Trivandrum Kerala India 695011
    88 HCG Manavata Cancer Centre Nashik Maharashtra India 422001
    89 Ruby Hall Clinic and Grant Medical Foundation Pune Maharashtra India 411001
    90 Deenanath Mangeshkar Hospital & Research Centre Pune Maharashtra India 411004
    91 Apollo Gleneagles Hospitals Kolkata Kolkata West Bengal India 700054
    92 Postgraduate Institute of Medical Education & Research Chandigarh India 160012
    93 Hadassah Medical Center Jerusalem Israel 9112001
    94 Rabin Medical Center Petach Tikva Israel 4941492
    95 Sheba Medical Center Ramat Gan Israel 5265602
    96 Istituto Nazionale dei Tumori Milano Lombardie Italy 20133
    97 Ospedale San Luca, IRCCS Istituto Auxologico Milano Milan Italy 20149
    98 Polic.Umberto I -Univ. La Sapienza Roma Rome Italy 00161
    99 A.O.U. Senese Policlinico Santa Maria alle Scotte Siena SI Italy 53100
    100 Istituto Oncologico Veneto IRCCS Padova Veneto Italy 35128
    101 Ospedale Garibaldi-Nesima Catania Italy 95122
    102 Azienda Ospedaliera Universitaria Federico II Napoli Italy 80131
    103 Azienda Ospedlaliero-Univeristaria Pisana, Stabilimento Ospedaliero di Cisanello Pisa Italy 56125
    104 I.F.O. Istituto Nazionale Tumori Regina Elena Roma Italy 00144
    105 Azienda Ospedaliero-Universitaria S.Giovanni Battista Torino Italy 10126
    106 Aichi Cancer Center Hospital Nagoya Aichi Japan 464-8681
    107 National Cancer Center Hospital East Kashiwa Chiba Japan 277-8577
    108 Hokkaido University Hospital Sapporo Hokkaido Japan 060-8648
    109 Kobe University Hospital Kobe Hyogo Japan 650-0017
    110 Yokohama City University Hospital Yokohama Kanagawa Japan 236-0004
    111 Osaka University Hospital Suita Osaka Japan 565-0871
    112 Japanese Foundation for Cancer Research Koto Tokyo Japan 135-8550
    113 National Hospital Organization Kyushu Medical Center Fukuoka Japan 810 8563
    114 National Cancer Center Goyang-si Gyeonggi-do Korea, Republic of 10408
    115 Seoul National University Bundang Hospital Seongnam-si Gyeonggi-do Korea, Republic of 13620
    116 Chonnam National University Hwasun Hospital Hwasun-gun Jeollanam Do Korea, Republic of 58128
    117 Seoul National University Hospital Seoul Seoul, Korea Korea, Republic of 03080
    118 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 03722
    119 Samsung Medical Center Seoul Korea, Republic of 06351
    120 Nederlands Kanker Instituut - Antoni van Leeuwenhoek Amsterdam Netherlands 1066 CX
    121 University Medical Center Groningen Groningen Netherlands 9713 GZ
    122 Leids Universitair Medisch Centrum Leiden Netherlands 2333 ZA
    123 Maastricht UMC+ Maastricht Netherlands 6229 HX
    124 Erasmus Medisch Centrum Rotterdam Netherlands 3015 GD
    125 Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Gliwice Poland 44 102
    126 Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej Kielce Poland 25-734
    127 National medical research center of radiology Obninsk Obninsk Kaluga Region Russian Federation 249036
    128 Clinic of advanced medical technologies n. a. Nicolay I. Pirogov (policlinic, hospital) Saint-Petersburg Northwestern Federal District Russian Federation 190020
    129 LLC Evimed Chelyabinsk Russian Federation 454048
    130 Blokhin Cancer Research Center Moscow Russian Federation 115478
    131 National Medical Research Center of Endocrinology of Ministry of Health Dept Moscow Russian Federation 117036
    132 Saint-Petersburg City Clinical Oncology Dispensary Saint-Petersburg Russian Federation 198255
    133 Hospital Universitario Virgen de la Victoria Malaga Andalucia Spain 29010
    134 Hospital Universitari Vall d'Hebron Barcelona Barcelona [Barcelona] Spain 8035
    135 Hospital Universitari de Girona Dr. Josep Trueta Girona Barcelona Spain 17007
    136 Hospital Universitario Ramón y Cajal Madrid Madrid, Comunidad De Spain 28034
    137 Clinica Universidad de Navarra Pamplona Navarra Spain 31008
    138 Clinica Universitaria De Navarra Pamplona Navarra Spain 31008
    139 Institut Catala d'Oncologia Barcelona Spain 08908
    140 Hospital General Universitario Gregorio Marañon Madrid Spain 28007
    141 Hospital Clinico San Carlos Madrid Spain 28040
    142 Hospital Universitario 12 de Octubre Madrid Spain 28041
    143 Hospital Universitario La Paz Madrid Spain 28046
    144 Hospital Universitario Miguel Servet Zaragoza Spain 50009
    145 China Medical University Hospital Taichung Taiwan 40447
    146 National Cheng-Kung Uni. Hosp. Tainan Taiwan 704
    147 National Taiwan University Hospital Taipei Taiwan 10048
    148 Gartnavel General Hospital Glasgow Glasgow City United Kingdom G12OYN
    149 University College Hospital - London London Greater London United Kingdom NW1 2PG
    150 Royal Marsden NHS Trust London Greater London United Kingdom SW3 6JJ
    151 Velindre Cancer Centre Cardiff South Glamorgan United Kingdom CF14 2TL
    152 Weston Park Hospital Sheffield South Yorkshire United Kingdom S10 2SJ
    153 Royal Marsden Hospital Sutton Surrey United Kingdom SM2 5PT
    154 Royal Marsden NHS Trust Sutton Surrey United Kingdom SM2 5PT

    Sponsors and Collaborators

    • Loxo Oncology, Inc.
    • Eli Lilly and Company

    Investigators

    • 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Loxo Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT04211337
    Other Study ID Numbers:
    • 17478
    • J2G-MC-JZJB
    • 2019-001978-28
    First Posted:
    Dec 26, 2019
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Loxo Oncology, Inc.
    medullary thyroid carcinoma
    targeted therapy
    Additional relevant MeSH terms:
    Thyroid Neoplasms
    Carcinoma, Neuroendocrine
    Thyroid Diseases

    Study Results

    No Results Posted as of Aug 19, 2022