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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04211337
Other study ID # 17478
Secondary ID J2G-MC-JZJB2019-
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date February 11, 2020
Est. completion date February 28, 2026

Study information

Verified date May 2024
Source Eli Lilly and Company
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

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.

Study Design


Intervention

Drug:
Selpercatinib
Administered orally
Cabozantinib
Administered orally
Vandetanib
Administered orally

Locations

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

Sponsors (2)

Lead Sponsor Collaborator
Loxo Oncology, Inc. Eli Lilly and Company

Countries where clinical trial is conducted

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, 

Outcome

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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