A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer
- Conditions
- Medullary Thyroid Cancer
- Interventions
- Registration Number
- NCT04211337
- Lead Sponsor
- Loxo Oncology, Inc.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 291
Not provided
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cabozantinib or Vandetanib - Treatment B (TRT B) Vandetanib 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 Selpercatinib - Treatment A (TRT A) Selpercatinib 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). Cabozantinib or Vandetanib - Treatment B (TRT B) Cabozantinib 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
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) Baseline to Progressive Disease or Death from Any Cause, Whichever Occurs First, Up to 39 Months 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.
- Secondary Outcome Measures
Name Time Method Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR) Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months 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).Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR Baseline through Disease Progression or Death Up to 39 Months 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.
Duration of Response (DoR) by BICR Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 39 Months 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.
Overall Survival (OS) Baseline 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.
PFS2 by Investigator Baseline 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.
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) Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months 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.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
Trial Locations
- Locations (141)
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
University of Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Hospital de Cancer de Londrina
🇧🇷Londrina, Paraná, Brazil
Fundação Pio XII - Hospital de Câncer de Barretos
🇧🇷Barretos, São Paulo, Brazil
University of Naples Federico II
🇮🇹Napoli, Campania, Italy
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Hospital de Clinicas de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Centre Georges François Leclerc
🇫🇷Dijon, Côte-d'Or, France
Grupo Oncoclínicas Botafogo
🇧🇷Rio de Janeiro, Brazil
Centre François Baclesse
🇫🇷Caen, Calvados, France
Hopital Claude Huriez - CHU de Lille
🇫🇷Lille, Nord, France
Otto-von-Guericke-Universität Magdeburg
🇩🇪Magdeburg, Sachsen-Anhalt, Germany
Azienda Ospedaliera Garibaldi
🇮🇹Catania, Italy
A. Tsyb Medical Radiological Research Center - branch of the National Medical Research Radiological
🇷🇺Obninsk, Kalužskaja Oblast', Russian Federation
University of Wisconsin Hospitals and Clinics
🇺🇸Madison, Wisconsin, United States
Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman
🇧🇪Liège, Belgium
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Gustave Roussy
🇫🇷Villejuif, Val-de-Marne, France
Hospital Sírio Libanês
🇧🇷Sao Paulo, São Paulo, Brazil
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Hämato-Onkologie Hamburg, Prof. Laack und Partner
🇩🇪Hamburg, Germany
Icesp - Instituto Do Câncer Do Estado de São Paulo
🇧🇷São Paulo, Brazil
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
🇫🇷Bordeaux, Aquitaine, France
Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne
🇫🇷Clermont-Ferrand, Puy-de-Dôme, France
European Interbalkan Medical Center
🇬🇷Thessaloníki, Thessaloniki, Greece
Azienda Ospedaliera Universitaria Pisana
🇮🇹Pisa, Toscana, Italy
Universitaetsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milan, Lombardia, Italy
Kobe University Hospital
🇯🇵Kobe, Hyogo, Japan
Chungbuk National University Hospital
🇰🇷Chungbuk, Chungcheongbuk-do [Chungbuk], Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Kyǒnggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Leids Universitair Medisch Centrum
🇳🇱Leiden, Zuid-Holland, Netherlands
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Charité Universitaetsmedizin Berlin - Campus Mitte
🇩🇪Berlin, Germany
Centre Leon Berard
🇫🇷Lyon, Rhône-Alpes, France
Universitätsmedizin Johannes Gutenberg Universität Mainz
🇩🇪Mainz, Rheinland-Pfalz, Germany
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
🇮🇹Torino, Piemonte, Italy
Aichi Cancer Center Hospital
🇯🇵Nagoya, Aichi, Japan
Osaka University Hospital
🇯🇵Suita, Osaka, Japan
National Hospital Organization Kyushu Medical Center
🇯🇵Fukuoka, Japan
HCG Manavata Cancer Centre
🇮🇳Nashik, Maharashtra, India
Hadassah Medical Center
🇮🇱Jerusalem, Yerushalayim, Israel
Yokohama City University Hospital
🇯🇵Yokohama, Kanagawa, Japan
Japanese Foundation for Cancer Research
🇯🇵Koto, Tokyo, Japan
Clinic Evimed
🇷🇺Chelyabinsk, Chelyabinskaya Oblast', Russian Federation
Endocrinology Research Center of Rosmedtechnologies
🇷🇺Moscow, Moskva, Russian Federation
Grant Medical Foundation - Ruby Hall Clinic
🇮🇳Pune, Maharashtra, India
Deenanath Mangeshkar Hospital & Research Centre
🇮🇳Pune, Maharashtra, India
Apollo Gleneagles Hospitals Kolkata
🇮🇳Kolkata, West Bengal, India
Weston Park Hospital
🇬🇧Sheffield, England, United Kingdom
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California Davis (UC Davis) Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
UCLA Hematology/Oncology - Westwood (Building 100)
🇺🇸Los Angeles, California, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Sir Charles Gairdner Hospital
🇦🇺Perth, Western Australia, Australia
Oncocentro
🇧🇷Belo Horizonte, Minas Gerais, Brazil
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Centro de Pesquisa Sao Lucas
🇧🇷Campinas, São Paulo, Brazil
Hospital de Clínicas de Ribeirão Preto
🇧🇷Ribeirão Preto, São Paulo, Brazil
Instituto D'Or de Pesquisa e Ensino (IDOR)
🇧🇷Sao Paulo, São Paulo, Brazil
Instituto Nacional de Câncer - INCA
🇧🇷Rio de Janeiro, Brazil
Grupo COI - Clínicas Oncológicas Integradas
🇧🇷Rio de Janeiro, Brazil
Centro Paulista de Oncologia Clínica
🇧🇷São Paulo, Brazil
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
Chongqing University Cancer Hospital
🇨🇳Chongqing, Chongqing, China
The First Affiliated Hospital Of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
Gansu Cancer Hospital
🇨🇳Lanzhou, Gansu, China
Beijing Tongren Hospital affiliated to Capital Medical University
🇨🇳Beijing, Beijing, China
Sun Yat-Sen University Cancer Centre
🇨🇳Guangzhou, Guangdong, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing, Jiangsu, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Jinan Central Hospital
🇨🇳Jinan, Shandong, China
West China Hospital, Sichuan University
🇨🇳Cheng Du, Sichuan, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Sir Run Run Shaw Hospital
🇨🇳Hangzhou, Zhejiang, China
First Affiliated Hospital of Kunming Medical University
🇨🇳Kunming, Yunnan, China
Zhejiang Provincial People's Hospital
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Fakultní nemocnice Brno Bohunice
🇨🇿Brno, Brno-město, Czechia
Fakultni nemocnice Motol
🇨🇿Praha, Praha 5, Czechia
Centre Paul Strauss
🇫🇷Strasbourg, Alsace, France
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Assistance Publique Hôpitaux de Marseille - Hôpital Nord
🇫🇷Marseille, Bouches-du-Rhône, France
Institut Claudius Regaud
🇫🇷Toulouse, Haute-Garonne, France
Centre Hospitalier Universitaire d'Angers
🇫🇷Angers, Maine-et-Loire, France
Pitie Salpetriere University Hospital
🇫🇷Paris, Orne, France
Klinikum der Universität München Großhadern
🇩🇪Würzburg, Bayern, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Niedersachsen, Germany
Alexandra Hospital
🇬🇷Athina, Attikí, Greece
Regional Cancer Centre - Thiruvananthapuram
🇮🇳Thiruvananthapuram, Kerala, India
University General Hospital of Heraklion
🇬🇷Heraklion, Irakleío, Greece
Rabin Medical Center
🇮🇱Petah-Tikva, HaMerkaz, Israel
Post Graduate Institute of Medical Education & Research (PGIMER)
🇮🇳Chandigarh, India
Sheba Medical Center
🇮🇱Ramat Gan, HaMerkaz, Israel
Policlinico Umberto I
🇮🇹Roma, Lazio, Italy
Istituto Auxologico Italiano
🇮🇹Milan, Milano, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹Rome, Roma, Italy
Ospedale Le Scotte
🇮🇹Siena, Toscana, Italy
Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Veneto, Italy
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Seoul National University Bundang Hospital
🇰🇷Seongnam, Kyǒnggi-do, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Maastricht UMC+
🇳🇱Maastricht, Limburg, Netherlands
Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)
🇳🇱Amsterdam, Noord-Holland, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Narodowy Instytut Onkologii - Oddzial w Gliwicach
🇵🇱Gliwice, Śląskie, Poland
Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej
🇵🇱Kielce, Świętokrzyskie, Poland
Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF
🇷🇺Moscow, Moskva, Russian Federation
Saint Petersburg State University
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Saint-Petersburg City Clinical Oncology Dispensary
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Instituto Catalan de Oncologia - Hospital Duran i Reynals
🇪🇸L'Hospitalet de Llobregat, Catalunya [Cataluña], Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Institut Català d'Oncologia (ICO) - Girona
🇪🇸Girona, Girona [Gerona], Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Malaga, Málaga, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
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
University College London Hospital
🇬🇧London, London, City Of, United Kingdom
Royal Marsden Hospital (Sutton)
🇬🇧London, Sutton, United Kingdom
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States