CS1008- in Combination With Sorafenib Compared to Sorafenib Alone in Subjects With Advanced Liver Cancer
6 de abril de 2021 actualizado por: Daiichi Sankyo, Inc.
Clinical Study Protocol Phase 2, Randomized Study of CS-1008 in Combination With Sorafenib Compared to Sorafenib Alone as First-Line Systemic Therapy in Subjects With Advanced Hepatocellular Carcinoma
The purpose of this study is to determine the safety and efficacy of CS-1008 in combination with sorafenib to sorafenib alone for treating liver cancer.
Approximately 160 participants will take part in this study at approximately 22 sites (4 in the US, 8 in Japan, and 10 in Asia).
Descripción general del estudio
Estado
Terminado
Tipo de estudio
Intervencionista
Inscripción (Actual)
172
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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Daegu, Corea, república de, 700-712
- Keimyung University Dongsan Hospital
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Seoul, Corea, república de, 135-710
- Samsung Medical Center
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Seoul, Corea, república de, 138-736
- Asan Medical Center
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Seoul, Corea, república de, 110-744
- Seoul National University Hospital
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Seoul, Corea, república de, 120-752
- Severance Hospital
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Seoul, Corea, república de, 136-705
- Korea University Anam Hospital
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Seoul, Corea, república de, 137-701
- Catholic Univ. of Korea, Seoul St. Mary's Hospital
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California
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Los Angeles, California, Estados Unidos, 90057
- Kenmar Research Group
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District of Columbia
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Washington, District of Columbia, Estados Unidos, 20007
- Georgetown-Lombardi Cancer Center
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New York
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New York, New York, Estados Unidos, 10029
- The Mount Sinai Medical Center
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37232
- Vanderbilt-Ingram Cancer Center
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Chiba, Japón, 260-8677
- Chiba University Hospital
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Okayama, Japón, 700-8558
- Okayama University Hospital
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Osaka, Japón, 537-8511
- Osaka Med Center Cancer and Cardiovascular Disease
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Tokyo, Japón, 180-8610
- Musashino Red-Cross Hospital
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Fukuoka
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Kurume-shi, Fukuoka, Japón, 830-0011
- Kurume University Hospital
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Hiroshima
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Hiroshima-city, Hiroshima, Japón
- Hiroshima University
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Ishikawa
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Kanazawa, Ishikawa, Japón
- Kanazawa University
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Osaka-sayama
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Osaka, Osaka-sayama, Japón, 589-8511
- Kinki University Hospital
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Yamaguchi
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Ube, Yamaguchi, Japón
- Yamaguchi University Hospital
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Changhua, Taiwán, 500
- Changhua Christian Hospital
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Chiayi City, Taiwán
- Chang Gung Memorial Hospital
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Kaohsiung, Taiwán, 807
- Kaohslung Medical University Hospital
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Tainan, Taiwán, 73657
- Chi-Mei Medical Center
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Tainan city, Taiwán, 704
- National Cheng-Kung University Hospital
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Taipei, Taiwán
- National Taiwan University Hospital
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Taoyuan, Taiwán, 33305
- Chang Gung Medical Foundation-Linkuo
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Niaosung Hsiang
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Kaohsiung, Niaosung Hsiang, Taiwán
- Kaohiung Chang Gung Hospital
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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
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
Histologically or cytologically confirmed hepatocellular carcinoma (HCC) or clinical diagnosis of HCC when the following criteria are all met:
- History of chronic hepatitis and/or cirrhosis of liver;
- Typical features of HCC demonstrated in dynamic imaging studies, such as three-phase computed tomography (CT); AND
- Alpha-fetoprotein (AFP) level > 200 ng/mL
Advanced diseases
- Extrahepatic metastasis, OR
- Locally advanced diseases which are not amenable for surgical resection or other loco-regional therapies including transhepatic arterial (chemo) embolization (TACE or TAE) and local ablative therapy
- Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 of at least 1 untreated target lesion that can be measured in 1 dimension
- At least 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Child-Pugh class A
- Life expectancy of at least 12 weeks
Adequate organ and bone marrow function as assessed by clinical laboratory evaluations:
- Hemoglobin ≥ 8.5 g/dL (transfusion and/or growth factor support allowed)
- Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
- Platelet count ≥ 75 x 10^9/L
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance > 40 mL/min
- Aspartate Aminotransferase (AST) and alkaline phosphatase ≤ 5.0 x ULN
- Total bilirubin ≤ 1.5 x ULN
- Serum amylase and lipase ≤ 1.5 x ULN
- Women of childbearing potential must be willing to consent to using effective contraception (eg, abstinence, hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device) while on treatment and for 3 months thereafter. Men who are the partner of a woman of childbearing potential must be willing to consent to using effective contraception (eg, vasectomy or barrier with spermicide) while on treatment and for 3 months thereafter
- All female participants of childbearing potential must have a negative pregnancy test (serum or urine) result
- Participants must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an International Review Board (IRB)/ Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) before the performance of any study specific procedures or tests
- Participants must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Exclusion Criteria:
- Any prior systemic therapy for HCC, including systemic chemotherapy (prior exposure to chemotherapy by TACE is allowed), immunotherapy, sorafenib or other Raf kinase inhibitors, Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptor (VEGFR)-inhibitors, epidermal growth factor receptor inhibitors or mechanistic target of rapamycin (mTOR) inhibitors
- Radiotherapy or major surgical procedure within 4 weeks of the screening/baseline visit or minor surgical procedures (eg, core biopsy or fine needle aspiration) within 2 weeks of the screening/baseline visit
- Anticipation of need for radiotherapy (RT) or a major surgical procedure during the study
- Any investigational agent within 4 weeks before the screening/baseline visit
History of any of the following conditions within 6 months before the screening/baseline visit:
- Myocardial infarction with significant impairment of cardiac function (eg, ejection fraction ≤ 30%)
- Severe/unstable angina pectoris
- New York Heart Association (NYHA) class III or intravenous (IV) congestive heart failure
- Clinically significant pulmonary disease (eg, severe chronic obstructive pulmonary disease or asthma)
- Clinically active brain metastases (defined as untreated, symptomatic or requiring steroids or anticonvulsants medications to control associated symptoms), uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis. Participants with treated brain metastasis will be included in the study if they have recovered from the acute, toxic effects of radiotherapy. A minimum of 15 days must have elapsed between the end of RT and the screening/baseline visit
- History of organ transplantation
- Clinically significant, severe, active infection requiring IV antibiotics
- Known history of human immunodeficiency virus (HIV) infection
- History of prior sensitivity reaction to any components of CS-1008 or sorafenib formulations
- History of a second malignancy, with the exception of in situ cervical cancer or adequately treated basal cell or squamous cell carcinoma of the skin
- Pregnant or breast feeding
- Serious intercurrent medical illnesses that, in the opinion of the Investigator, would impair the participant's ability to provide informed consent or unacceptably reduce the safety of the proposed treatment
- Clinically significant (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] grade ≥ 3) gastrointestinal bleeding in the past 12 months or current active gastrointestinal bleeding
- Presence of esophageal varices at risk of bleeding, such as large esophageal/gastric varices or those with red sign, or active peptic ulcer with or without exposed vessels at risk of bleeding (as documented by endoscopy)
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 6 months
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: Safety Cohort 1 CS-1008 and Sorafenib
Combination of CS-1008 and sorafenib; CS-1008 (2 mg/kg per week) in combination with sorafenib (400 mg self-administered by mouth twice daily) over 4 weeks observation, and may continue treatment until progression.
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On a once a week basis CS-1008 will be administered intravenously starting at 2 mg/kg.
On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day.
The total daily dose of sorafenib is 800 mg.
The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
Otros nombres:
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Experimental: Safety Cohort 2 CS-1008 and Sorafenib
Combination of CS-1008 and sorafenib; CS-1008 (4 mg/kg per week) in combination with sorafenib (400 mg self-administered by mouth twice daily) over 4 weeks observation, and may continue treatment until progression.
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On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day.
The total daily dose of sorafenib is 800 mg.
The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
Otros nombres:
On a once a week basis CS-1008 will be administered intravenously at 4 mg/kg if tolerated.
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Comparador activo: Safety Cohort 3 CS-1008 and Sorafenib
Combination of CS-1008 and sorafenib; CS-1008 (6 mg/kg per week) in combination with sorafenib (400 mg self-administered by mouth twice daily) over 4 weeks observation, and may continue treatment until progression.
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On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day.
The total daily dose of sorafenib is 800 mg.
The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
Otros nombres:
On a once a week basis CS-1008 will be administered intravenously at 6 mg/kg if tolerated.
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Experimental: Treatment Group 1 CS-1008 and Sorafenib
Combination of CS-1008 and sorafenib.
Treatment Group 1: CS-1008 (6 mg/kg [or as determined] loading, 2 mg/kg/week maintenance) + sorafenib twice daily (N=50)
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On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day.
The total daily dose of sorafenib is 800 mg.
The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
Otros nombres:
A 6 mg/kg loading dose of CS-1008 will be administered intravenously, followed by a 2 mg/kg/week maintenance dose on a once-a-week basis.
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Experimental: Treatment Group 2 with CS-1008 and Sorafenib
Combination of CS-1008 and sorafenib.
Treatment Group 2: CS-1008 (6 mg/kg [or as determined] loading, 6 mg/kg/week [or maximum tolerated dose {MTD}] maintenance) + sorafenib twice daily (N=50)
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On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day.
The total daily dose of sorafenib is 800 mg.
The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
Otros nombres:
A 6 mg/kg loading dose of CS-1008 will be administered intravenously, followed by a 6 mg/kg/week maintenance dose on a once-a-week basis.
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Experimental: Treatment Group 3 with Sorafenib Alone
Sorafenib.
Treatment Group 3: sorafenib twice daily (N=50)
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On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day.
The total daily dose of sorafenib is 800 mg.
The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
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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Time to Progression (TTP) Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
Periodo de tiempo: Baseline up to approximately 2 years post-dose.
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Time to progression was defined as the time from randomization to the date of the first objective documentation of radiographic or symptomatic progression, whichever came first.
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Baseline up to approximately 2 years post-dose.
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Overall Survival Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
Periodo de tiempo: Baseline up to approximately 3 years 2 months post-dose.
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Overall survival (OS) was defined as the time from randomization to the date of death.
The factors in the final model were treatment, Eastern Cooperative Oncology Group (ECOG) performance status, presence of extrahepatic metastasis and/or macrovessel invasion, and region.
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Baseline up to approximately 3 years 2 months post-dose.
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Best Overall Response and Objective Response Rate Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
Periodo de tiempo: Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 3 years 2 months post-dose.
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The best overall response is the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], unconfirmed CR, unconfirmed PR, stable disease [SD], and progressive disease [PD]) among all overall responses recorded from the start of treatment until the participant withdraws from the study based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
If there is no tumor assessment after the first dose of study drug, the best overall response is classified as Inevaluable.
CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions.
Objective response rate was defined as confirmed CR and confirmed PR.
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Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 3 years 2 months post-dose.
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Treatment-Emergent Adverse Events Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
Periodo de tiempo: Baseline up to 30 days after last dose, up to approximately 3 years 2 months post-dose.
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Treatment-Emergent Adverse Events (TEAEs) were defined as those adverse events (AEs) that occurred, having been absent before the study, or worsened in severity after the initiation of study treatment administration.
An AE that occurred more than 30 days after the last dose of study medication was not included as a TEAE unless it was considered related to treatment or the assessment of relatedness was missing.
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Baseline up to 30 days after last dose, up to approximately 3 years 2 months post-dose.
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
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)
9 de julio de 2010
Finalización primaria (Actual)
13 de julio de 2012
Finalización del estudio (Actual)
9 de septiembre de 2013
Fechas de registro del estudio
Enviado por primera vez
15 de diciembre de 2009
Primero enviado que cumplió con los criterios de control de calidad
15 de diciembre de 2009
Publicado por primera vez (Estimar)
16 de diciembre de 2009
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
8 de abril de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
6 de abril de 2021
Última verificación
1 de abril de 2021
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Digestivo
- Neoplasias por tipo histológico
- Neoplasias
- Neoplasias por sitio
- Adenocarcinoma
- Neoplasias Glandulares y Epiteliales
- Neoplasias del Sistema Digestivo
- Enfermedades del HIGADO
- Carcinoma
- Carcinoma Hepatocelular
- Neoplasias Hepaticas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antineoplásicos
- Inhibidores de la proteína quinasa
- Sorafenib
Otros números de identificación del estudio
- CS1008-A-U204
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.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
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