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

NCT ID: NCT04211337

Last Updated: 2025-04-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

291 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-11

Study Completion Date

2026-02-28

Brief Summary

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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

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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.

Conditions

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Medullary Thyroid Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cabozantinib or Vandetanib - Treatment B (TRT B)

140 mg Cabozantinib administered orally daily (QD) or 300 mg Vandetanib administered orally QD per physician choice.

Cabozantinib Adolescent Dose: 40 mg/m2.

Vandetanib Adolescent Dose:

* 0.7 - \<0.9 - 100 mg every other day (QOD)
* 0.9 - \<1.2 - 100 mg QD
* 1.2 - \<1.6 - 7-day schedule 100 mg - 200 mg - 100 mg - 200 mg - 100 mg - 200 mg - 100 mg
* ≥1.6 - 200 QD

Group Type ACTIVE_COMPARATOR

Cabozantinib

Intervention Type DRUG

Administered orally

Vandetanib

Intervention Type DRUG

Administered orally

Selpercatinib - Treatment A (TRT A)

160 milligrams Selpercatinib administered orally (PO) twice daily (BID).

Adolescent Dose: 92 milligrams per square meter (mg/m2) BID (not to exceed 160 mg BID).

Group Type EXPERIMENTAL

Selpercatinib

Intervention Type DRUG

Administered orally

Interventions

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Selpercatinib

Administered orally

Intervention Type DRUG

Cabozantinib

Administered orally

Intervention Type DRUG

Vandetanib

Administered orally

Intervention Type DRUG

Other Intervention Names

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LY3527723 LOXO-292

Eligibility Criteria

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Inclusion Criteria

* 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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role collaborator

Loxo Oncology, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

UCLA Hematology/Oncology - Westwood (Building 100)

Los Angeles, California, United States

Site Status

University of California Davis (UC Davis) Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Wisconsin Hospitals and Clinics

Madison, Wisconsin, United States

Site Status

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital

Perth, Western Australia, Australia

Site Status

Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman

Liège, , Belgium

Site Status

Oncocentro

Belo Horizonte, Minas Gerais, Brazil

Site Status

Hospital de Cancer de Londrina

Londrina, Paraná, Brazil

Site Status

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Fundação Pio XII - Hospital de Câncer de Barretos

Barretos, São Paulo, Brazil

Site Status

Centro de Pesquisa Sao Lucas

Campinas, São Paulo, Brazil

Site Status

Hospital de Clínicas de Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

Site Status

Hospital Sírio Libanês

São Paulo, São Paulo, Brazil

Site Status

Instituto D'Or de Pesquisa e Ensino (IDOR)

São Paulo, São Paulo, Brazil

Site Status

Instituto Nacional de Câncer - INCA

Rio de Janeiro, , Brazil

Site Status

Grupo Oncoclínicas Botafogo

Rio de Janeiro, , Brazil

Site Status

Grupo COI - Clínicas Oncológicas Integradas

Rio de Janeiro, , Brazil

Site Status

Icesp - Instituto Do Câncer Do Estado de São Paulo

São Paulo, , Brazil

Site Status

Centro Paulista de Oncologia Clínica

São Paulo, , Brazil

Site Status

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Anhui Provincial Hospital

Hefei, Anhui, China

Site Status

Beijing Tongren Hospital affiliated to Capital Medical University

Beijing, Beijing Municipality, China

Site Status

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

Site Status

The First Affiliated Hospital Of Fujian Medical University

Fuzhou, Fujian, China

Site Status

Gansu Cancer Hospital

Lanzhou, Gansu, China

Site Status

Sun Yat-Sen University Cancer Centre

Guangzhou, Guangdong, China

Site Status

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Site Status

Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School

Nanjing, Jiangsu, China

Site Status

Jilin Cancer Hospital

Changchun, Jilin, China

Site Status

Jinan Central Hospital

Jinan, Shandong, China

Site Status

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

Site Status

First Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, China

Site Status

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, China

Site Status

Sir Run Run Shaw Hospital

Hangzhou, Zhejiang, China

Site Status

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Site Status

Fakultní nemocnice Brno Bohunice

Brno, Brno-město, Czechia

Site Status

Fakultni nemocnice Motol

Prague, Praha 5, Czechia

Site Status

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Site Status

Centre Paul Strauss

Strasbourg, Alsace, France

Site Status

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Bordeaux, Aquitaine, France

Site Status

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, France

Site Status

Assistance Publique Hôpitaux de Marseille - Hôpital Nord

Marseille, Bouches-du-Rhône, France

Site Status

Centre François Baclesse

Caen, Calvados, France

Site Status

Centre Georges François Leclerc

Dijon, Côte-d'Or, France

Site Status

Institut Claudius Regaud

Toulouse, Haute-Garonne, France

Site Status

Centre Hospitalier Universitaire d'Angers

Angers, Maine-et-Loire, France

Site Status

Hopital Claude Huriez - CHU de Lille

Lille, Nord, France

Site Status

Pitie Salpetriere University Hospital

Paris, Orne, France

Site Status

Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne

Clermont-Ferrand, Puy-de-Dôme, France

Site Status

Gustave Roussy

Villejuif, Val-de-Marne, France

Site Status

Klinikum der Universität München Großhadern

München, Bavaria, Germany

Site Status

Klinikum der Universität München Großhadern

Würzburg, Bavaria, Germany

Site Status

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Site Status

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Site Status

Universitätsmedizin Johannes Gutenberg Universität Mainz

Mainz, Rhineland-Palatinate, Germany

Site Status

Otto-von-Guericke-Universität Magdeburg

Magdeburg, Saxony-Anhalt, Germany

Site Status

Charité Universitaetsmedizin Berlin - Campus Mitte

Berlin, , Germany

Site Status

Hämato-Onkologie Hamburg, Prof. Laack und Partner

Hamburg, , Germany

Site Status

Alexandra Hospital

Athens, Attikí, Greece

Site Status

University General Hospital of Heraklion

Heraklion, Irakleío, Greece

Site Status

European Interbalkan Medical Center

Thessaloniki, Thessaloniki, Greece

Site Status

Regional Cancer Centre - Thiruvananthapuram

Thiruvananthapuram, Kerala, India

Site Status

HCG Manavata Cancer Centre

Nashik, Maharashtra, India

Site Status

Grant Medical Foundation - Ruby Hall Clinic

Pune, Maharashtra, India

Site Status

Deenanath Mangeshkar Hospital & Research Centre

Pune, Maharashtra, India

Site Status

Apollo Gleneagles Hospitals Kolkata

Kolkata, West Bengal, India

Site Status

Post Graduate Institute of Medical Education & Research (PGIMER)

Chandigarh, , India

Site Status

Rabin Medical Center

Petah Tikva, Central District, Israel

Site Status

Sheba Medical Center

Ramat Gan, Central District, Israel

Site Status

Hadassah Medical Center

Jerusalem, Jerusalem, Israel

Site Status

University of Naples Federico II

Napoli, Campania, Italy

Site Status

Policlinico Umberto I

Rome, Lazio, Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, Italy

Site Status

Istituto Auxologico Italiano

Milan, Milano, Italy

Site Status

Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Site Status

Istituto Nazionale Tumori Regina Elena

Rome, Roma, Italy

Site Status

Azienda Ospedaliera Universitaria Pisana

Pisa, Tuscany, Italy

Site Status

Ospedale Le Scotte

Siena, Tuscany, Italy

Site Status

Istituto Oncologico Veneto IRCCS

Padua, Veneto, Italy

Site Status

Azienda Ospedaliera Garibaldi

Catania, , Italy

Site Status

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, Japan

Site Status

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Site Status

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Site Status

Kobe University Hospital

Kobe, Hyōgo, Japan

Site Status

Yokohama City University Hospital

Yokohama, Kanagawa, Japan

Site Status

Osaka University Hospital

Suita, Osaka, Japan

Site Status

Japanese Foundation for Cancer Research

Koto, Tokyo, Japan

Site Status

National Hospital Organization Kyushu Medical Center

Fukuoka, , Japan

Site Status

Maastricht UMC+

Maastricht, Limburg, Netherlands

Site Status

Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)

Amsterdam, North Holland, Netherlands

Site Status

Leids Universitair Medisch Centrum

Leiden, South Holland, Netherlands

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

Narodowy Instytut Onkologii - Oddzial w Gliwicach

Gliwice, Silesian Voivodeship, Poland

Site Status

Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej

Kielce, Świętokrzyskie Voivodeship, Poland

Site Status

Clinic Evimed

Chelyabinsk, Chelyabinsk Oblast, Russia

Site Status

A. Tsyb Medical Radiological Research Center - branch of the National Medical Research Radiological

Obninsk, Kalužskaja Oblast', Russia

Site Status

Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF

Moscow, Moscow, Russia

Site Status

Endocrinology Research Center of Rosmedtechnologies

Moscow, Moscow, Russia

Site Status

Saint Petersburg State University

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

Saint-Petersburg City Clinical Oncology Dispensary

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

Chungbuk National University Hospital

Jungbuk, Chungcheongbuk-do [Chungbuk], South Korea

Site Status

National Cancer Center

Goyang-si, Kyǒnggi-do, South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam, Kyǒnggi-do, South Korea

Site Status

Seoul National University Hospital

Seoul, Seoul-teukbyeolsi [Seoul], South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, Seoul-teukbyeolsi [Seoul], South Korea

Site Status

Samsung Medical Center

Seoul, Seoul-teukbyeolsi [Seoul], South Korea

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [Barcelona], Spain

Site Status

Instituto Catalan de Oncologia - Hospital Duran i Reynals

L'Hospitalet de Llobregat, Catalunya [Cataluña], Spain

Site Status

Institut Català d'Oncologia (ICO) - Girona

Girona, Girona [Gerona], Spain

Site Status

Clinica Universidad de Navarra

Madrid, Madrid, Comunidad de, Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Comunidad de, Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, Madrid, Comunidad de, Spain

Site Status

Hospital Universitario La Paz

Madrid, Madrid, Comunidad de, Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, Málaga, Spain

Site Status

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Site Status

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Site Status

Hospital Clinico San Carlos

Madrid, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Velindre Cancer Centre

Cardiff, Cardiff [Caerdydd Gb-crd], United Kingdom

Site Status

Weston Park Hospital

Sheffield, England, United Kingdom

Site Status

Gartnavel General Hospital

Glasgow, Glasgow City, United Kingdom

Site Status

Royal Marsden Hospital (Chelsea)

London, Kensington and Chelsea, United Kingdom

Site Status

University College London Hospital

London, London, City of, United Kingdom

Site Status

Royal Marsden Hospital (Sutton)

London, Sutton, United Kingdom

Site Status

Countries

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United States Australia Belgium Brazil Canada China Czechia France Germany Greece India Israel Italy Japan Netherlands Poland Russia South Korea Spain United Kingdom

References

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Hadoux J, Elisei R, Brose MS, Hoff AO, Robinson BG, Gao M, Jarzab B, Isaev P, Kopeckova K, Wadsley J, Fuhrer D, Keam B, Bardet S, Sherman EJ, Tahara M, Hu MI, Singh R, Lin Y, Soldatenkova V, Wright J, Lin B, Maeda P, Capdevila J, Wirth LJ; LIBRETTO-531 Trial Investigators. Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. N Engl J Med. 2023 Nov 16;389(20):1851-1861. doi: 10.1056/NEJMoa2309719. Epub 2023 Oct 21.

Reference Type DERIVED
PMID: 37870969 (View on PubMed)

Wirth LJ, Brose MS, Elisei R, Capdevila J, Hoff AO, Hu MI, Tahara M, Robinson B, Gao M, Xia M, Maeda P, Sherman E. LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naive RET-mutant medullary thyroid cancer. Future Oncol. 2022 Sep;18(28):3143-3150. doi: 10.2217/fon-2022-0657. Epub 2022 Aug 15.

Reference Type DERIVED
PMID: 35969032 (View on PubMed)

Jaber T, Dadu R, Hu MI. Medullary thyroid carcinoma. Curr Opin Endocrinol Diabetes Obes. 2021 Oct 1;28(5):540-546. doi: 10.1097/MED.0000000000000662.

Reference Type DERIVED
PMID: 34292174 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://trials.lillytrialguide.com/en-US/trial/MAk6ymq4v0xp57E7leZ7P

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

Other Identifiers

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J2G-MC-JZJB

Identifier Type: OTHER

Identifier Source: secondary_id

2019-001978-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17478

Identifier Type: -

Identifier Source: org_study_id

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