Un estudio que evalúa la combinación de encorafenib y cetuximab versus irinotecán/cetuximab o infusión de 5-fluorouracilo (5-FU)/ácido folínico (FA)/irinotecán (FOLFIRI)/cetuximab en pacientes chinos con cáncer colorrectal metastásico mutante BRAF V600E. (NAUTICALCRC)
8 de abril de 2026 actualizado por: Pierre Fabre Medicament
Un estudio de fase II multicéntrico, aleatorizado, abierto, de dos brazos, con una fase inicial de seguridad que evalúa la combinación de encorafenib y cetuximab frente a irinotecán/cetuximab o 5-fluorouracilo (5-FU)/ácido folínico (FA) en infusión /Irinotecan (FOLFIRI)/Cetuximab en pacientes chinos con cáncer colorrectal metastásico mutante BRAF V600E.
Encorafenib se está desarrollando actualmente (con o sin binimetinib), en combinación con cetuximab, para el tratamiento de pacientes adultos con cáncer colorrectal metastásico (CCRm) con mutación de serina/treonina quinasa V600E (BRAF V600E) del protooncogén B-RAF, que tienen recibido tratamiento sistémico previo.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
107
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Beijing Municipality
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Beijing, Beijing Municipality, Porcelana, 100730
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
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Beijing, Beijing Municipality, Porcelana, 100036
- Beijing Cancer Hospital
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Fujian
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Fuzhou, Fujian, Porcelana, 350014
- Fujian Medical University - Fujian Provincial Cancer Hospital
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Xiamen, Fujian, Porcelana, 361001
- The First Affiliated Hospital of Xiamen University
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Guangdong
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Foshan, Guangdong, Porcelana, 528010
- The First People's Hospital of Foshan
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Guangzhou, Guangdong, Porcelana, 510095
- Cancer Center of Guangzhou Medical University
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Guangzhou, Guangdong, Porcelana, 510655
- The Sixth Affiliated Hospital Sun Yat-sen University
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Shantou, Guangdong, Porcelana, 515041
- Cancer Hospital Affiliated to Shantou University Medical College
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Shenzhen, Guangdong, Porcelana, 518036
- Peking University Shenzhen Hospital
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Hebei
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Baoding, Hebei, Porcelana, 071000
- The Affiliated Hospital of Hebei University
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Heilongjiang
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Harbin, Heilongjiang, Porcelana, 150040
- Harbin Medical University Cancer Hospital
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Henan
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Zhengzhou, Henan, Porcelana, 450052
- The First Affiliated Hospital of Zhengzhou University
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Zhengzhou, Henan, Porcelana, 450008
- Henan Cancer Hospital
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Hubei
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Wuhan, Hubei, Porcelana, 430071
- Zhongnan Hospital of Wuhan University
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Wuhan, Hubei, Porcelana, 430022
- Union Hospital Tongji Medical College Huazhong University Of Science And Technology
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Wuhan, Hubei, Porcelana, 430030
- Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
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Hunan
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Changsha, Hunan, Porcelana, 410008
- Xiangya Hospital Central South University
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Jiangsu
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Changzhou, Jiangsu, Porcelana, 213003
- The First People's Hospital of Changzhou
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Jiangxi
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Ganzhou, Jiangxi, Porcelana, 341001
- First Affiliated Hospital of Gannan Medical University
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Nanchang, Jiangxi, Porcelana, 330006
- The First Affiliated Hospital of Nanchang University
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Nanchang, Jiangxi, Porcelana, 330006
- The Second Affiliated Hospital of Nanchang University
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Jilin
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Changchun, Jilin, Porcelana, 130021
- The First Hospital of Jilin University
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Liaoning
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Jinzhou, Liaoning, Porcelana, 121011
- The First Affiliated Hospital of Jinzhou Medical University
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Shenyang, Liaoning, Porcelana, 110001
- The First Hospital of China Medical University
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Shenyang, Liaoning, Porcelana, 110042
- Liaoning Cancer Hospital & Institute
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Shaanxi
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Xi'an, Shaanxi, Porcelana, 710068
- Shaanxi Provincial People's Hospital
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Porcelana, 200032
- Zhongshan Hospital Fudan University
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Shanghai, Shanghai Municipality, Porcelana, 200040
- Huashan Hospital Fudan University
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Shanghai, Shanghai Municipality, Porcelana, 200092
- Xinhua Hospital Affilliated to Shanghai Jiaotong University School of Medicine
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Shanghai, Shanghai Municipality, Porcelana, 200120
- Shanghai East Hospital, Tongji University
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Sichuan
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Neijiang, Sichuan, Porcelana, 641000
- The Second People's Hospital of Neijiang
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Tianjin Municipality
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Tianjin, Tianjin Municipality, Porcelana, 300060
- Tianjin Medical University Cancer Institute and Hospital
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Zhejiang
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Hangzhou, Zhejiang, Porcelana, 310003
- The First Affiliated Hospital - Zhejiang University School of Medicine
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Hangzhou, Zhejiang, Porcelana, 310016
- Sir Run Run Shaw Hospital - Zhejiang University School of Medicine
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Descripción
Criterios de inclusión para la preselección molecular:
Se deben cumplir los siguientes criterios de inclusión para que un participante sea elegible para someterse a un examen molecular previo de tumores:
- Participante masculino o femenino chino con edad ≥18 años en el momento del consentimiento informado.
- Cáncer colorrectal (CCR) confirmado histológica o citológicamente que es metastásico.
- Elegible para recibir cetuximab según la etiqueta aprobada en China con respecto al estado de mutación del homólogo del oncogén viral (RAS) del sarcoma de rata tumoral (es decir, aprobado para el estado Rat Sarcoma Viral Oncogene Homologue Wild Type (RAS wt)).
- Capaz de proporcionar una cantidad suficiente de muestras tumorales representativas para las pruebas de laboratorio prospectivo central del protooncogén B-RAF, el estado de mutación de la serina/treonina quinasa (BRAF) y también el estado retrospectivo de RAS wt y las pruebas de inestabilidad de microsatélites (MSI).
Criterios de inclusión para el período de tratamiento:
Los siguientes criterios de inclusión deben cumplirse para que un participante sea elegible para este estudio:
- Participante masculino o femenino chino con edad ≥18 años en el momento del consentimiento informado.
- CCR confirmado histológica o citológicamente que es metastásico e irresecable en el momento del ingreso al estudio (es decir, no apto para la resección quirúrgica completa en la selección).
- Presencia de una mutación BRAF V600E en tejido tumoral previamente determinada por un ensayo local en cualquier momento antes de la selección o por el laboratorio central.
NOTA: Es posible que se apliquen otros criterios de inclusión definidos en el protocolo
Criterios de exclusión para la preselección molecular:
Los participantes que cumplan cualquiera de los siguientes criterios no son elegibles para someterse a un examen molecular previo de tumores:
- Tratamiento previo anti-receptor del factor de crecimiento epidérmico (anti-EGFR)
- Más de dos regímenes previos en el entorno metastásico.
- Contraindicación conocida para recibir cetuximab o irinotecán a la dosis planificada de acuerdo con la etiqueta local más reciente de cetuximab e irinotecán.
- Antecedentes conocidos del síndrome de Gilbert o se sabe que tiene cualquiera de los siguientes genotipos: uridina 5'-difosfo-glucuronosiltransferasa (UGT) 1A1*6/*6, UGT1A1*28/*28 o UGT1A1*6/*28.
- Enfermedad leptomeníngea.
Criterios de exclusión para el período de tratamiento:
- Tratamiento previo con cualquier inhibidor del protooncogén serina/treonina-proteína quinasa (RAF), cetuximab, panitumumab u otros inhibidores de EGFR.
- Metástasis cerebral sintomática.
- Enfermedad leptomeníngea.
- Uso de cualquier medicamento/suplemento a base de hierbas o cualquier medicamento o alimento que sea un inhibidor o inductor moderado o fuerte del citocromo P450 (CYP) 3A4/5 ≤ 1 semana antes del inicio de la intervención del estudio.
- Antecedentes conocidos de pancreatitis aguda o crónica dentro de los 6 meses anteriores al inicio de la intervención del estudio.
NOTA: Es posible que se apliquen otros criterios de exclusión definidos en el protocolo
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Encorafenib y cetuximab
Fase de introducción de seguridad (SLI): Ciclos de 28 días de encorafenib una vez al día (QD) 300 mg (4 cápsulas orales de 75 mg) y cetuximab 400 mg/m² dosis inicial (infusión de 120 minutos), luego 250 mg/m² (infusión de 60 minutos) a partir de entonces una vez por semana Fase aleatoria (fase II): Ciclos de 28 días de encorafenib una vez al día (QD) 300 mg (4 cápsulas orales de 75 mg) y cetuximab 400 mg/m² dosis inicial (infusión de 120 minutos), luego 250 mg/m² (infusión de 60 minutos) a partir de entonces una vez por semana |
cápsula dura oral
Otros nombres:
infusión intravenosa
Otros nombres:
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Experimental: Irinotecan y cetuximab o FOLFIRI y cetuximab
Fase aleatoria (fase II): irinotecán y cetuximab o FOLFIRI y cetuximab en ciclos de 28 días. Irinotecán y cetuximab:
O FOLFIRI y cetuximab:
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cápsula dura oral
Otros nombres:
infusión intravenosa
Otros nombres:
Combinación de: irinotecán (también conocido como: camptosar, camptotecina-11 y CPT-11) infusión intravenosa, ácido folínico (también conocido como: ácido 5-formiltetrahidrofólico y leucovorina) infusión intravenosa y 5-FU (también conocido como fluorouracilo) bolo intravenoso /infusión intravenosa
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Safety Lead-in Phase (SLI): Incidence of Dose Limiting Toxicities (DLTs)
Periodo de tiempo: Cycle 1 (up to 28 days)
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DLT rate was estimated based on data from DLT-evaluable participants during the DLT-evaluation period (which is the first 28 days after the first dose of study intervention in the SLI) to assess the safety and tolerability of the doublet arm.
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Cycle 1 (up to 28 days)
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Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Primary Completion Date
Periodo de tiempo: From first dose to the earliest documented progression or death due to any cause, with a minimal participant's follow-up of 36 weeks and a maximum treatment exposure of 68 weeks
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PFS was defined as the time from the date of randomization to the earliest documented disease progression (PD) as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause.
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From first dose to the earliest documented progression or death due to any cause, with a minimal participant's follow-up of 36 weeks and a maximum treatment exposure of 68 weeks
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Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Final Analysis
Periodo de tiempo: From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
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PFS was defined as the time from the date of randomization to the earliest documented disease progression as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause.
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From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per BICR
Periodo de tiempo: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks
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cORR as determined by Blinded (to treatment received) Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per Investigator
Periodo de tiempo: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks
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cORR as determined by investigator assessment per RECIST version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Duration of Response (DOR) Per BICR
Periodo de tiempo: From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
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DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by BICR per RECIST Version 1.1, or death due to any cause.
PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
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From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Duration of Response (DOR) Per Investigator
Periodo de tiempo: From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
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DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by investigator assessment per RECIST Version 1.1, or death due to any cause.
PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
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From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Overall Duration of Exposure to Study Treatment
Periodo de tiempo: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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Exposure to the study intervention was defined as the time interval between the actual date of first study intervention administration (included) and the actual date of last study intervention administration (included), i.e., as the quantity "date of last study intervention administration date of first study intervention administration + 1 day".
Duration of exposure by treatment arm was computed as the maximum of all durations of exposure for each drug of the assigned regimen.
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Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Periodo de tiempo: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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A TEAE is any untoward medical occurrence in a participant temporally associated with the use of study drug, whether or not considered related to the study drug.
Number of participants reporting TEAEs were reported in this outcome measure.
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Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Serious TEAEs
Periodo de tiempo: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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A serious TEAE is a TEAE that results in significant health consequences, such as death, hospitalization, or permanent disability.
Number of participants reporting serious TEAEs were reported in this outcome measure.
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Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs)
Periodo de tiempo: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 68 weeks
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An AE is any untoward medical occurrence in a participant, whether or not considered related to the study intervention.
Number of participants with dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure.
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Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 68 weeks
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Safety Lead-in Phase: Number of Participants With Clinically Notable Vital Sign Abnormalities
Periodo de tiempo: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Clinically notable changes were defined as participants meeting the elevated or low values criterion compared to baseline.
The criterion for clinically notable elevated values included: systolic blood pressure (BP): ≥ 160 millimeters of mercury (mmHg) and an increase ≥ 20 mmHg from baseline; diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; weight (kg) increase from baseline of ≥ 10 percent; body temperature [degree Celsius (deg C)] ≥ 37.5 deg C. The criterion for clinically notable low values included: systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; weight: ≥ 20 percent decrease from baseline; body temperature [deg C]: ≤ 36 °C.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values
Periodo de tiempo: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Clinically notable ECG changes were defined as participants meeting the criterion for QT interval, QT interval corrected for heart rate using Fridericia's formula (QTcF), and heart rate compared to baseline.
The criterion for QT interval and QTcF included: increase from baseline > 30 msec (ms); increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms.
The criterion for heart rate included: increase from baseline > 25 percent to a value > 100 beats per minute (bpm), decrease from baseline > 25 percent and to a value < 50 bpm.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters
Periodo de tiempo: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Clinically notable shift was defined as a worsening from baseline by at least 2 Grades, or to Grade 3 or above based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03.
'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease.
'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase.
Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters
Periodo de tiempo: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Clinically notable shift was defined as a worsening from baseline by at least 2 Grades, or to Grade 3 or above based on NCI-CTCAE version 4.03.
'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease.
'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase.
Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Notable Dermatological Abnormalities
Periodo de tiempo: From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 111 weeks
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Dermatological examination was performed to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and primary melanoma, as these have been reported to occur with selective B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor treatment.
[1] The category "Other" includes all other dermatological findings identified during examination (e.g.
rash acneiform, skin hyperpigmentation...).
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From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Measurement of Performance Status Using the Eastern Co-operative Oncology Group (ECOG) Scale
Periodo de tiempo: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 68 weeks
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The performance status of participants was assessed using the Eastern Co-operative Oncology Group (ECOG) scale.
The scale was defined with the range from 0 to 5 with lower score mean a lower functional impairment, and a higher score (e.g. 5) corresponding to death.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 68 weeks
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Safety Lead-in Phase: Evaluation of the Plasma Concentrations of Encorafenib
Periodo de tiempo: First day of treatment (Cycle 1 Day I) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
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First day of treatment (Cycle 1 Day I) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Safety Lead-in Phase: Evaluation of the Serum Concentrations of Cetuximab
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
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First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Safety Lead-in Phase: Evaluation of the Area Under the Curve (AUC) Derived From Plasma Concentration of Encorafenib
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
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First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Safety Lead-in Phase: Evaluation of the Area Under the Curve (AUC) Derived From Serum Concentration of Cetuximab
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
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First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Safety Lead-in Phase: Evaluation of the Maximum Concentration (Cmax) Derived From Plasma Concentration of Encorafenib
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
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First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Safety Lead-in Phase: Evaluation of the Maximum Concentration (Cmax) Derived From Serum Concentration of Cetuximab
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
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First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Safety Lead-in Phase: Evaluation of the Minimum Concentration (Cmin) Derived From Plasma Concentration of Encorafenib
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
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First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Safety Lead-in Phase: Evaluation of the Minimum Concentration (Cmin) Derived From Serum Concentration of Cetuximab
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
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First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
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Randomized Phase 2: Progression-free Survival (PFS) by Investigator
Periodo de tiempo: From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
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PFS was defined as the time from the date of randomization to the earliest documented date of PD as determined by investigator assessment per RECIST Version 1.1, or death due to any cause.
PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
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From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Confirmed Objective Response Rate (cORR) in ENCO + CETUX Arm vs Control Arm Per BICR
Periodo de tiempo: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
cORR as determined by Blinded (to treatment received) Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
|
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Confirmed Objective Response Rate (cORR) in ENCO + CETUX Arm vs Control Arm Per Investigator
Periodo de tiempo: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
cORR as determined by investigator assessment per RECIST Version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
|
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Duration of Response (DOR) in ENCO + CETUX Arm vs Control Arm Per BICR
Periodo de tiempo: From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
|
DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by BICR per RECIST Version 1.1, or death due to any cause.
PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
|
From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Duration of Response (DOR) in ENCO + CETUX Arm vs Control Arm Per Investigator
Periodo de tiempo: From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
|
DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by investigator assessment per RECIST Version 1.1, or death due to any cause.
PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
|
From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Confirmed Disease Control Rate (cDCR) in ENCO + CETUX Arm vs Control Arm Per BICR
Periodo de tiempo: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
cDCR was defined as the proportion of participants with a confirmed Best Overall Response (BOR) of CR, PR or Stable Disease (SD), as determined by BICR per RECIST Version 1.1.
CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
|
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Confirmed Disease Control Rate (cDCR) in ENCO + CETUX Arm vs Control Arm Per Investigator
Periodo de tiempo: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
cDCR was defined as the proportion of participants with a confirmed Best Overall Response (BOR) of CR, PR or Stable Disease (SD), as determined by investigator assesment per RECIST Version 1.1.
CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
|
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Time to Response (TTR) in ENCO + CETUX Arm vs Control Arm Per BICR
Periodo de tiempo: From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
|
TTR for confirmed responses was defined for responders (CR or PR) as the time between the date of randomization until the first documented response of CR or PR as determined by BICR per RECIST Version 1.1.
CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
|
From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Time to Response (TTR) in ENCO + CETUX Arm vs Control Arm Per Investigator
Periodo de tiempo: From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
|
TTR for confirmed responses was defined for responders (CR or PR) as the time between the date of randomization until the first documented response of CR or PR as determined by investigator assessment per RECIST Version 1.1.
CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
|
From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Overall Survival (OS)
Periodo de tiempo: From randomization to death due to any cause, with a maximum treatment exposure of 116 weeks
|
OS was defined as time from randomization until date of death due to any cause.
|
From randomization to death due to any cause, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Overall Duration of Exposure to Study Treatment
Periodo de tiempo: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 116 weeks
|
Exposure to the study intervention was defined as the time interval between the actual date of first study intervention administration (included) and the actual date of last study intervention administration (included), i.e., as the quantity "date of last study intervention administration date of first study intervention administration + 1 day".
Duration of exposure by treatment arm was computed as the maximum of all durations of exposure for each drug of the assigned regimen.
|
Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Periodo de tiempo: Day 1 until 30 days after study intervention discontinuation
|
A TEAE is any untoward medical occurrence in a participant temporally associated with the use of study drug, whether or not considered related to the study drug.
Number of participants reporting TEAEs were reported in this outcome measure.
|
Day 1 until 30 days after study intervention discontinuation
|
|
Randomized Phase 2: Number of Participants With Serious TEAEs
Periodo de tiempo: Day 1 until 30 days after study intervention discontinuation
|
A serious TEAE is a TEAE that results in significant health consequences, such as death, hospitalization, or permanent disability.
Number of participants reporting serious TEAEs were reported in this outcome measure.
|
Day 1 until 30 days after study intervention discontinuation
|
|
Randomized Phase 2: Number of Participants With Clinically Notable Vital Sign Abnormalities
Periodo de tiempo: Day 1 until 30 days after last dose of study treatment
|
Clinically notable changes were defined as participants meeting the elevated or low values criterion compared to baseline.
The criterion for clinically notable elevated values included: systolic blood pressure (BP): ≥ 160 millimeters of mercury (mmHg) and an increase ≥ 20 mmHg from baseline; diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; weight (kg) increase from baseline of ≥ 10 percent; body temperature [degree Celsius (deg C)] ≥ 37.5 deg C. The criterion for clinically notable low values included: systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; weight: ≥ 20 percent decrease from baseline; body temperature [deg C]: ≤ 36 °C.
|
Day 1 until 30 days after last dose of study treatment
|
|
Randomized Phase 2: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values
Periodo de tiempo: Day 1 until 30 days after last dose of study treatment
|
Clinically notable ECG changes were defined as participants meeting the criterion for QT interval, QT interval corrected for heart rate using Fridericia's formula (QTcF), and heart rate compared to baseline.
The criterion for QT interval and QTcF included: increase from baseline > 30 msec (ms); increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms.
The criterion for heart rate included: increase from baseline > 25 percent to a value > 100 beats per minute (bpm), decrease from baseline > 25 percent and to a value < 50 bpm.
|
Day 1 until 30 days after last dose of study treatment
|
|
Randomized Phase 2: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters
Periodo de tiempo: Day 1 until 30 days after last dose of study treatment
|
Clinically notable shift was defined as a worsening from baseline by at least 2 grades, or to grade 3 or above based on NCI-CTCAE version 4.03.
'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease.
'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase.
Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death.
|
Day 1 until 30 days after last dose of study treatment
|
|
Randomized Phase 2: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters
Periodo de tiempo: Day 1 until 30 days after last dose of study treatment
|
Clinically notable shift was defined as a worsening from baseline by at least 2 grades, or to grade 3 or above based on NCI-CTCAE version 4.03.
'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease.
'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase.
Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death.
|
Day 1 until 30 days after last dose of study treatment
|
|
Randomized Phase 2: Number of Participants With Notable Dermatological Abnormalities
Periodo de tiempo: From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 116 weeks
|
Dermatological examination was performed to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and primary melanoma, as these have been reported to occur with selective B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor treatment.
[1] All other dermatological findings identified during examination (e.g.
rash acneiform, skin hyperpigmentation...).
|
From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Measurement of Performance Status Using the Eastern Co-operative Oncology Group (ECOG) Scale
Periodo de tiempo: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 116 weeks
|
The performance status of participants was assessed using the Eastern Co-operative Oncology Group (ECOG) scale.
The scale was defined with the range from 0 to 5 with lower score mean a lower functional impairment, and a higher score (e.g. 5) corresponding to death.
[1] Participants with no assessment of ECOG in the time frame.
|
Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Time to Definitive Deterioration in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) Questionnaire Scores
Periodo de tiempo: Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) questionnaire consisted of nine multi-item scales: five functional scales (physical, role, cognitive, emotional and social); three symptom scales (fatigue, pain, nausea and vomiting); and a global health and Quality of Life (QoL) scale.
Each scale in the questionnaire was scored (0 to 100).
High scores represented a high health/quality of life.
Time to definitive deterioration (at least 10% worsening relative to Baseline with no later improvement) was assessed for both randomized phase treatment arms.
|
Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Time to Definitive Deterioration in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire
Periodo de tiempo: Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
The European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) consisted of the EQ-5D descriptive system and the EQ visual analogue scale (VAS).
The descriptive system consisted of five dimension (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), each was rated according to a five-point verbal rating scale (VRS): 1. no problems, 2. slight problems, 3. moderate problems, 4. severe problems and 5. extreme problems) and translated into a five-digit number that described the participant's health state.
Time to definitive deterioration (at least 10% worsening relative to Baseline with no later improvement) was assessed for both randomized phase treatment arms.
|
Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Time to Definitive Deterioration in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) Questionnaire
Periodo de tiempo: Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
The Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) was a validated quality of life questionnaire for patient reported outcome assessment.
The Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) consisted of 36 items, presented on a five-point Likert scale, in four domains of well-being (physical, emotional, social and functional) and the Colorectal Cancer Subscale.
Higher score reflects a better quality of life.
Time to definitive deterioration (at least 10% worsening relative to Baseline with no later improvement) was assessed for both randomized phase treatment arms.
|
Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Evolution in the Patient Global Impression of Change (PGIC) Questionnaire
Periodo de tiempo: Cycle 2 Day 1 until 30 days safety follow-up
|
The Patient Global Impression of Change (PGIC) questionnaire is a scale often used to anchor and characterize participant reported outcome (PRO) findings.
This consisted of questions that asked participants to evaluate their colorectal cancer symptoms since starting study intervention according to a seven-point verbal rating scale: 1. very much improved, 2. much improved, 3. minimally improved, 4. no change, 5. minimally worse, 6. much worse, 7. very much worse.
Completions of questionnaire are summarized per treatment group and study visits.
Number of participants analyzed correspond to the actual number of participants who completed the questionnaire at the corresponding visit.
|
Cycle 2 Day 1 until 30 days safety follow-up
|
|
Randomized Phase 2: Evaluation of the Plasma Concentrations of Encorafenib
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Serum Concentrations of Cetuximab
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Area Under the Curve (AUC) Derived From Plasma Concentration of Encorafenib
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Area Under the Curve (AUC) Derived From Serum Concentration of Cetuximab
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Minimum Concentration (Cmin) Derived From Plasma Concentration of Encorafenib
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Minimum Concentration (Cmin) Derived From Serum Concentration of Cetuximab
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Maximum Concentration (Cmax) Derived From Plasma Concentration of Encorafenib
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Maximum Concentration (Cmax) Derived From Serum Concentration of Cetuximab
Periodo de tiempo: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Otras medidas de resultado
Medida de resultado |
Periodo de tiempo |
|---|---|
|
Fase 2 aleatorizada: cambios desde el inicio en el antígeno carcinoembrionario (CEA) y el antígeno del cáncer 19-9 (CA19-9) en sangre al comienzo de cada ciclo y al final del tratamiento
Periodo de tiempo: Cribado (Día -28 a -1) hasta la finalización del estudio, aproximadamente de 12 a 29 meses
|
Cribado (Día -28 a -1) hasta la finalización del estudio, aproximadamente de 12 a 29 meses
|
|
Fase 2 aleatorizada: estado de inestabilidad de microsatélites (MSI) en muestras fijadas con formalina e incluidas en parafina (FFPE) utilizando ensayos establecidos de reacción en cadena de la polimerasa (PCR) en muestra de tumor versus control de línea germinal en la selección
Periodo de tiempo: Cribado (Día -28 a Día -1)
|
Cribado (Día -28 a Día -1)
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Shen Lin, MD, Peking University Cancer Hospital & Institute
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
14 de septiembre de 2021
Finalización primaria (Actual)
19 de diciembre de 2023
Finalización del estudio (Actual)
7 de diciembre de 2024
Fechas de registro del estudio
Enviado por primera vez
30 de abril de 2021
Primero enviado que cumplió con los criterios de control de calidad
5 de agosto de 2021
Publicado por primera vez (Actual)
13 de agosto de 2021
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
30 de abril de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
8 de abril de 2026
Última verificación
1 de febrero de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias por sitio
- Neoplasias
- Enfermedades intestinales
- Neoplasias Gastrointestinales
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Enfermedades Gastrointestinales
- Neoplasias Intestinales
- Enfermedades Rectales
- Enfermedades del Colon
- Neoplasias colorrectales
- Aminoácidos, péptidos y proteínas
- Proteínas
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Compuestos heterocíclicos, 2 anillos
- Compuestos heterocíclicos, anillo fusionado
- Campeptecina
- Alcaloides
- Enzimas y coenzimas
- Anticuerpos, monoclonales, humanizados
- Anticuerpos, monoclonal
- Anticuerpos
- Inmunoglobulinas
- Inmunoproteínas
- Proteínas de la sangre
- Globulinas séricas
- Globulinas
- Pirimidinas
- Formiltetrahidrofolatos
- Tetrahidrofolatos
- Ácido fólico
- Pterins
- Pteridinas
- Uracílico
- Pirimidinonas
- Coenzimas
- Irinotecán
- Cetuximab
- Fluorouracilo
- Leucovorina
- encorafenib
- Protocolo IFL
Otros números de identificación del estudio
- W00090GE202
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
producto fabricado y exportado desde los EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .