Clinical trial NCT04211337: A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Medullary Thyroid Cancer
Keywords: medullary thyroid carcinoma
targeted therapy
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2019-12-26
Enrollment: 291
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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: 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.

Eligibility 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 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.

Primary outcomes:
measure: Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)
timeFrame: Baseline to Progressive Disease or Death from Any Cause, Whichever Occurs First, Up to 39 Months
Secondary outcomes:
measure: Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR)
timeFrame: Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months
measure: Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR
timeFrame: Baseline through Disease Progression or Death Up to 39 Months
measure: Duration of Response (DoR) by BICR
timeFrame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 39 Months
measure: Overall Survival (OS)
timeFrame: Baseline
measure: PFS2 by Investigator
timeFrame: Baseline
measure: Comparative Tolerability: Number of Weeks With High Side Effect Bother Based Score of 3 or 4 on the Functional Assessment of Cancer Therapy Item GP5 (FACT-GP5)
timeFrame: Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months
measure: 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)
timeFrame: Baseline
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology - Westwood (Building 100)
state: California
city: Sacramento
country: United States
facility: University of California Davis (UC Davis) Comprehensive Cancer Center
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Columbus
country: United States
facility: The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospitals and Clinics
state: Wisconsin
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman
city: Belo Horizonte
country: Brazil
facility: Oncocentro
state: Minas Gerais
city: Londrina
country: Brazil
facility: Hospital de Cancer de Londrina
state: Paraná
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Fundação Pio XII - Hospital de Câncer de Barretos
state: São Paulo
city: Campinas
country: Brazil
facility: Centro de Pesquisa Sao Lucas
state: São Paulo
city: Ribeirão Preto
country: Brazil
facility: Hospital de Clínicas de Ribeirão Preto
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Sírio Libanês
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto D'Or de Pesquisa e Ensino (IDOR)
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Câncer - INCA
city: Rio de Janeiro
country: Brazil
facility: Grupo Oncoclínicas Botafogo
city: Rio de Janeiro
country: Brazil
facility: Grupo COI - Clínicas Oncológicas Integradas
city: São Paulo
country: Brazil
facility: Icesp - Instituto Do Câncer Do Estado de São Paulo
city: São Paulo
country: Brazil
facility: Centro Paulista de Oncologia Clínica
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Tongren Hospital affiliated to Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: The First Affiliated Hospital Of Fujian Medical University
state: Fujian
city: Lanzhou
country: China
facility: Gansu Cancer Hospital
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Centre
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Cheng Du
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno Bohunice
state: Brno-město
city: Praha
country: Czechia
facility: Fakultni nemocnice Motol
state: Praha 5
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Strasbourg
country: France
facility: Centre Paul Strauss
state: Alsace
city: Bordeaux
country: France
facility: Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
state: Aquitaine
city: Marseille
country: France
facility: Assistance Publique Hôpitaux de Marseille - Hôpital Nord
state: Bouches-du-Rhône
city: Caen
country: France
facility: Centre François Baclesse
state: Calvados
city: Dijon
country: France
facility: Centre Georges François Leclerc
state: Côte-d'Or
city: Toulouse
country: France
facility: Institut Claudius Regaud
state: Haute-Garonne
city: Angers
country: France
facility: Centre Hospitalier Universitaire d'Angers
state: Maine-et-Loire
city: Lille
country: France
facility: Hopital Claude Huriez - CHU de Lille
state: Nord
city: Paris
country: France
facility: Pitie Salpetriere University Hospital
state: Orne
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne
state: Puy-de-Dôme
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhône-Alpes
city: Villejuif
country: France
facility: Gustave Roussy
state: Val-de-Marne
city: München
country: Germany
facility: Klinikum der Universität München Großhadern
state: Bayern
city: Würzburg
country: Germany
facility: Klinikum der Universität München Großhadern
state: Bayern
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Universitätsmedizin Johannes Gutenberg Universität Mainz
state: Rheinland-Pfalz
city: Magdeburg
country: Germany
facility: Otto-von-Guericke-Universität Magdeburg
state: Sachsen-Anhalt
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin - Campus Mitte
city: Hamburg
country: Germany
facility: Hämato-Onkologie Hamburg, Prof. Laack und Partner
city: Athina
country: Greece
facility: Alexandra Hospital
state: Attikí
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion
state: Irakleío
city: Thessaloníki
country: Greece
facility: European Interbalkan Medical Center
state: Thessaloniki
city: Thiruvananthapuram
country: India
facility: Regional Cancer Centre - Thiruvananthapuram
state: Kerala
city: Nashik
country: India
facility: HCG Manavata Cancer Centre
state: Maharashtra
city: Pune
country: India
facility: Grant Medical Foundation - Ruby Hall Clinic
state: Maharashtra
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Centre
state: Maharashtra
city: Kolkata
country: India
facility: Apollo Gleneagles Hospitals Kolkata
state: West Bengal
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education & Research (PGIMER)
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
state: HaMerkaz
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
state: Yerushalayim
city: Napoli
country: Italy
facility: University of Naples Federico II
state: Campania
city: Roma
country: Italy
facility: Policlinico Umberto I
state: Lazio
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: Lombardia
city: Milan
country: Italy
facility: Istituto Auxologico Italiano
state: Milano
city: Torino
country: Italy
facility: Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
state: Piemonte
city: Rome
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
state: Roma
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
state: Toscana
city: Siena
country: Italy
facility: Ospedale Le Scotte
state: Toscana
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS
state: Veneto
city: Catania
country: Italy
facility: Azienda Ospedaliera Garibaldi
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Yokohama
country: Japan
facility: Yokohama City University Hospital
state: Kanagawa
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Koto
country: Japan
facility: Japanese Foundation for Cancer Research
state: Tokyo
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center
city: Chungbuk
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbuk-do [Chungbuk]
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Kyǒnggi-do
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Kyǒnggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul-teukbyeolsi [Seoul]
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
state: Limburg
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)
state: Noord-Holland
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii - Oddzial w Gliwicach
state: Śląskie
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej
state: Świętokrzyskie
city: Chelyabinsk
country: Russian Federation
facility: Clinic Evimed
state: Chelyabinskaya Oblast'
city: Obninsk
country: Russian Federation
facility: A. Tsyb Medical Radiological Research Center - branch of the National Medical Research Radiological
state: Kalužskaja Oblast'
city: Moscow
country: Russian Federation
facility: Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF
state: Moskva
city: Moscow
country: Russian Federation
facility: Endocrinology Research Center of Rosmedtechnologies
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State University
state: Sankt-Peterburg
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg City Clinical Oncology Dispensary
state: Sankt-Peterburg
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [Barcelona]
city: L'Hospitalet de Llobregat
country: Spain
facility: Instituto Catalan de Oncologia - Hospital Duran i Reynals
state: Catalunya [Cataluña]
city: Girona
country: Spain
facility: Institut Català d'Oncologia (ICO) - Girona
state: Girona [Gerona]
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
state: Madrid, Comunidad De
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
state: Málaga
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
state: Cardiff [Caerdydd Gb-crd]
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
state: England
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital
state: Glasgow City
city: London
country: United Kingdom
facility: Royal Marsden Hospital (Chelsea)
state: Kensington And Chelsea
city: London
country: United Kingdom
facility: University College London Hospital
state: London, City Of
city: London
country: United Kingdom
facility: Royal Marsden Hospital (Sutton)
state: Sutton
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.