Medullary Thyroid Cancer Clinical Trial
— LIBRETTO-531Official 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)
Verified date | May 2024 |
Source | Eli Lilly and Company |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 291 |
Est. completion date | February 28, 2026 |
Est. primary completion date | May 22, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 12 Years and older |
Eligibility | - 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. |
Country | Name | City | State |
---|---|---|---|
Australia | Peter MacCallum Cancer Centre | Melbourne | Victoria |
Australia | The Alfred Hospital | Melbourne | Victoria |
Australia | Sir Charles Gairdner Hospital | Perth | Western Australia |
Australia | Royal North Shore Hospital | St Leonards | New South Wales |
Belgium | Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman | Liège | |
Brazil | Fundação Pio XII - Hospital de Câncer de Barretos | Barretos | São Paulo |
Brazil | Oncocentro | Belo Horizonte | Minas Gerais |
Brazil | Centro de Pesquisa Sao Lucas | Campinas | São Paulo |
Brazil | Hospital de Cancer de Londrina | Londrina | Paraná |
Brazil | Hospital de Clinicas de Porto Alegre | Porto Alegre | Rio Grande Do Sul |
Brazil | Hospital de Clínicas de Ribeirão Preto | Ribeirão Preto | São Paulo |
Brazil | Grupo COI - Clínicas Oncológicas Integradas | Rio de Janeiro | |
Brazil | Grupo Oncoclínicas Botafogo | Rio de Janeiro | |
Brazil | Instituto Nacional de Câncer - INCA | Rio de Janeiro | |
Brazil | Hospital Sírio Libanês | Sao Paulo | São Paulo |
Brazil | Instituto D'Or de Pesquisa e Ensino (IDOR) | Sao Paulo | São Paulo |
Brazil | Centro Paulista de Oncologia Clínica | São Paulo | |
Brazil | Icesp - Instituto Do Câncer Do Estado de São Paulo | São Paulo | |
Canada | Princess Margaret Cancer Centre | Toronto | Ontario |
China | Beijing Tongren Hospital affiliated to Capital Medical University | Beijing | Beijing |
China | Jilin Cancer Hospital | Changchun | Jilin |
China | Hunan Cancer Hospital | Changsha | Hunan |
China | West China Hospital, Sichuan University | Cheng Du | Sichuan |
China | Chongqing University Cancer Hospital | Chongqing | Chongqing |
China | The First Affiliated Hospital Of Fujian Medical University | Fuzhou | Fujian |
China | Sun Yat-Sen University Cancer Centre | Guangzhou | Guangdong |
China | Sir Run Run Shaw Hospital | Hangzhou | Zhejiang |
China | Zhejiang Cancer Hospital | Hangzhou | Zhejiang |
China | Zhejiang Provincial People's Hospital | Hangzhou | Zhejiang |
China | Harbin Medical University Cancer Hospital | Harbin | Heilongjiang |
China | Anhui Provincial Hospital | Hefei | Anhui |
China | Jinan Central Hospital | Jinan | Shandong |
China | First Affiliated Hospital of Kunming Medical University | Kunming | Yunnan |
China | Gansu Cancer Hospital | Lanzhou | Gansu |
China | Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School | Nanjing | Jiangsu |
China | Fudan University Shanghai Cancer Center | Shanghai | Shanghai |
China | Tianjin Medical University Cancer Institute and Hospital | Tianjin | Tianjin |
China | Henan Cancer Hospital | Zhengzhou | Henan |
Czechia | Fakultní nemocnice Brno Bohunice | Brno | Brno-mesto |
Czechia | Fakultni nemocnice Olomouc | Olomouc | |
Czechia | Fakultni nemocnice Motol | Praha | Praha 5 |
France | Centre Hospitalier Universitaire d'Angers | Angers | Maine-et-Loire |
France | Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest | Bordeaux | Aquitaine |
France | Centre François Baclesse | Caen | Calvados |
France | Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne | Clermont-Ferrand | Puy-de-Dôme |
France | Centre Georges François Leclerc | Dijon | Côte-d'Or |
France | Hopital Claude Huriez - CHU de Lille | Lille | Nord |
France | Centre Leon Berard | Lyon | Rhône-Alpes |
France | Assistance Publique Hôpitaux de Marseille - Hôpital Nord | Marseille | Bouches-du-Rhône |
France | Pitie Salpetriere University Hospital | Paris | Orne |
France | Centre Paul Strauss | Strasbourg | Alsace |
France | Institut Claudius Regaud | Toulouse | Haute-Garonne |
France | Gustave Roussy | Villejuif | Val-de-Marne |
Germany | Charité Universitaetsmedizin Berlin - Campus Mitte | Berlin | |
Germany | Universitaetsklinikum Essen | Essen | Nordrhein-Westfalen |
Germany | Hämato-Onkologie Hamburg, Prof. Laack und Partner | Hamburg | |
Germany | Medizinische Hochschule Hannover | Hannover | Niedersachsen |
Germany | Otto-von-Guericke-Universität Magdeburg | Magdeburg | Sachsen-Anhalt |
Germany | Universitätsmedizin Johannes Gutenberg Universität Mainz | Mainz | Rheinland-Pfalz |
Germany | Klinikum der Universität München Großhadern | München | Bayern |
Germany | Klinikum der Universität München Großhadern | Würzburg | Bayern |
Greece | Alexandra Hospital | Athina | Attikí |
Greece | University General Hospital of Heraklion | Heraklion | Irakleío |
Greece | European Interbalkan Medical Center | Thessaloníki | Thessaloniki |
India | Post Graduate Institute of Medical Education & Research (PGIMER) | Chandigarh | |
India | Apollo Gleneagles Hospitals Kolkata | Kolkata | West Bengal |
India | HCG Manavata Cancer Centre | Nashik | Maharashtra |
India | Deenanath Mangeshkar Hospital & Research Centre | Pune | Maharashtra |
India | Grant Medical Foundation - Ruby Hall Clinic | Pune | Maharashtra |
India | Regional Cancer Centre - Thiruvananthapuram | Thiruvananthapuram | Kerala |
Israel | Hadassah Medical Center | Jerusalem | Yerushalayim |
Israel | Rabin Medical Center | Petah-Tikva | HaMerkaz |
Israel | Sheba Medical Center | Ramat Gan | HaMerkaz |
Italy | Azienda Ospedaliera Garibaldi | Catania | |
Italy | Fondazione IRCCS Istituto Nazionale dei Tumori | Milan | Lombardia |
Italy | Istituto Auxologico Italiano | Milan | Milano |
Italy | University of Naples Federico II | Napoli | Campania |
Italy | Istituto Oncologico Veneto IRCCS | Padova | Veneto |
Italy | Azienda Ospedaliera Universitaria Pisana | Pisa | Toscana |
Italy | Policlinico Umberto I | Roma | Lazio |
Italy | Istituto Nazionale Tumori Regina Elena | Rome | Roma |
Italy | Ospedale Le Scotte | Siena | Toscana |
Italy | Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino | Torino | Piemonte |
Japan | National Hospital Organization Kyushu Medical Center | Fukuoka | |
Japan | National Cancer Center Hospital East | Kashiwa | Chiba |
Japan | Kobe University Hospital | Kobe | Hyogo |
Japan | Japanese Foundation for Cancer Research | Koto | Tokyo |
Japan | Aichi Cancer Center Hospital | Nagoya | Aichi |
Japan | Hokkaido University Hospital | Sapporo | Hokkaido |
Japan | Osaka University Hospital | Suita | Osaka |
Japan | Yokohama City University Hospital | Yokohama | Kanagawa |
Korea, Republic of | Chungbuk National University Hospital | Chungbuk | Chungcheongbuk-do [Chungbuk] |
Korea, Republic of | National Cancer Center | Goyang-si | Kyonggi-do |
Korea, Republic of | Seoul National University Bundang Hospital | Seongnam | Kyonggi-do |
Korea, Republic of | Samsung Medical Center | Seoul | Seoul-teukbyeolsi [Seoul] |
Korea, Republic of | Seoul National University Hospital | Seoul | Seoul-teukbyeolsi [Seoul] |
Korea, Republic of | Severance Hospital, Yonsei University Health System | Seoul | Seoul-teukbyeolsi [Seoul] |
Netherlands | Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL) | Amsterdam | Noord-Holland |
Netherlands | University Medical Center Groningen | Groningen | |
Netherlands | Leids Universitair Medisch Centrum | Leiden | Zuid-Holland |
Netherlands | Maastricht UMC+ | Maastricht | Limburg |
Poland | Narodowy Instytut Onkologii - Oddzial w Gliwicach | Gliwice | Slaskie |
Poland | Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej | Kielce | Swietokrzyskie |
Russian Federation | Clinic Evimed | Chelyabinsk | Chelyabinskaya Oblast' |
Russian Federation | Endocrinology Research Center of Rosmedtechnologies | Moscow | Moskva |
Russian Federation | Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF | Moscow | Moskva |
Russian Federation | A. Tsyb Medical Radiological Research Center - branch of the National Medical Research Radiological | Obninsk | Kalužskaja Oblast' |
Russian Federation | Saint Petersburg State University | Saint Petersburg | Sankt-Peterburg |
Russian Federation | Saint-Petersburg City Clinical Oncology Dispensary | Saint Petersburg | Sankt-Peterburg |
Spain | Hospital Universitari Vall d'Hebron | Barcelona | Barcelona [Barcelona] |
Spain | Institut Català d'Oncologia (ICO) - Girona | Girona | Girona [Gerona] |
Spain | Instituto Catalan de Oncologia - Hospital Duran i Reynals | L'Hospitalet de Llobregat | Catalunya [Cataluña] |
Spain | Clinica Universidad de Navarra | Madrid | Madrid, Comunidad De |
Spain | Hospital Clinico San Carlos | Madrid | |
Spain | Hospital General Universitario Gregorio Marañon | Madrid | |
Spain | Hospital Universitario 12 de Octubre | Madrid | Madrid, Comunidad De |
Spain | Hospital Universitario La Paz | Madrid | Madrid, Comunidad De |
Spain | Hospital Universitario Ramón y Cajal | Madrid | Madrid, Comunidad De |
Spain | Hospital Universitario Virgen de la Victoria | Malaga | Málaga |
Spain | Clinica Universidad de Navarra | Pamplona | Navarra |
Spain | Hospital Universitario Miguel Servet | Zaragoza | |
United Kingdom | Velindre Cancer Centre | Cardiff | Cardiff [Caerdydd Gb-crd] |
United Kingdom | Gartnavel General Hospital | Glasgow | Glasgow City |
United Kingdom | Royal Marsden Hospital (Chelsea) | London | Kensington And Chelsea |
United Kingdom | Royal Marsden Hospital (Sutton) | London | Sutton |
United Kingdom | University College London Hospital | London | London, City Of |
United Kingdom | Weston Park Hospital | Sheffield | England |
United States | University of Michigan | Ann Arbor | Michigan |
United States | Emory University | Atlanta | Georgia |
United States | University of Alabama at Birmingham | Birmingham | Alabama |
United States | Massachusetts General Hospital | Boston | Massachusetts |
United States | University of Chicago Medical Center | Chicago | Illinois |
United States | University of Cincinnati Medical Center | Cincinnati | Ohio |
United States | The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center | Columbus | Ohio |
United States | City of Hope National Medical Center | Duarte | California |
United States | University of Texas MD Anderson Cancer Center | Houston | Texas |
United States | UCLA Hematology/Oncology - Westwood (Building 100) | Los Angeles | California |
United States | University of Wisconsin Hospitals and Clinics | Madison | Wisconsin |
United States | Memorial Sloan Kettering Cancer Center | New York | New York |
United States | Thomas Jefferson University | Philadelphia | Pennsylvania |
United States | University of Pennsylvania Hospital | Philadelphia | Pennsylvania |
United States | University of California Davis (UC Davis) Comprehensive Cancer Center | Sacramento | California |
United States | Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center | Torrance | California |
Lead Sponsor | Collaborator |
---|---|
Loxo Oncology, Inc. | Eli Lilly and Company |
United States, Australia, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, India, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) | PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria, or death from any cause in the absence of BICR-documented progressive disease.
Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. |
Baseline to Progressive Disease or Death from Any Cause, Whichever Occurs First, Up to 35 Months | |
Secondary | Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR) | TFFS by BICR is defined as the time from randomization to the first occurrence of:
documented radiographic disease progression per RECIST 1.1 as assessed by BICR; or unacceptable toxicity leading to treatment discontinuation as assessed by the investigator. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. To qualify as an event, the toxicity must be from an intolerable AE (defined as any study drug-related AE that meets protocol guidance for treatment discontinuation, with the exception of alopecia); or death (due to any cause). |
Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 35 Months | |
Secondary | Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR | ORR is defined as the number of participants who achieved the best overall response (BOR) of CR or PR divided by the total number of participants randomized to each treatment arm. ORR per RECIST 1.1 as assessed by BICR. | Baseline through Disease Progression or Death up to 35 months | |
Secondary | Duration of Response (DoR) by BICR | DoR by BICR is defined as the time from the date that measurement criteria for complete response (CR) or partial response (PR) (whichever is first recorded) are first met by the BICR or investigator assessment, as applicable, until the first date that disease is recurrent or documented disease progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of documented disease progression or recurrence. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. | Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 33 Months | |
Secondary | Overall Survival (OS) | Overall survival (OS) is defined as the time from randomization until death from any cause. If the participant is alive or lost to follow-up at the time of data analysis, OS data will be censored on the last date the participant is known to be alive. | Baseline to Date of Death from Any Cause Up to 36 Months | |
Secondary | PFS2 by Investigator | Progression-free survival 2 (PFS2) is defined as the time from randomization to disease progression (radiographic or symptomatic progression as determined by the investigator) on the next line of treatment or death from any cause in the absence of observed disease progression. If the participant is alive at the cutoff for analysis, and disease progression has not been observed, PFS2 data will be censored on the latest date of last progression-free assessment or start of the next line of treatment. | Baseline to Second Disease Progression or Death from Any Cause Up to 35 Months | |
Secondary | 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) | Comparative tolerability defined as a comparison of the proportion of time on treatment with high side effect bother as assessed by the FACT-GP5. The FACT-GP5 is a single question used to assess the overall bother of the treatment side effects. It is scored using a 5-point rating scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; and 4 = very much), where lower scores reflect less bother from treatment side effects.
Time with high side effect bother (i.e.) score of 3 or 4 is reported here and was derived as follows: cumulative amount of time, in weeks, during which a participant reports high side effect bother divided by the total duration of therapy (weeks), derived as (date of last study treatment dose - date of first study treatment dose + 1) divided by 7. |
Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 35 Months | |
Secondary | 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 |
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