- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT04947826
Combination Therapy of HAIC and HLX10 and HLX04 in HCC With Major Portal Vein Tumor Thrombosis
A Randomized, Double-blinded, Controlled Phase II Study of Combination Therapy of HAIC (Hepatic Arterial Infusion Chemotherapy), HLX10 (PD-1 Antibody) and HLX04 (VEGF Antibody) Compared With HAIC and Placebo in Hepatocellular Carcinoma With Major Portal Vein Tumor Thrombosis
Descripción general del estudio
Estado
Tipo de estudio
Inscripción (Anticipado)
Fase
- Fase 2
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Willing to attend the study and having given the ICF
- Age ≥18
- Have a HCC diagnosis confirmed by radiology, histology, or cytology
- HCC is diagnosed at Barcelona Clinic Liver Cancer (BCLC) Stage C with major portal vein tumor thrombosis ( VP3~4, or Cheng's II~IV)
- Have not accepted any of systemic therapy for HCC such as systemic chemotherapy, molecular targeted drugs, immunotherapy.
- At least 1 measurable intrahepatic lesion suitable for repeat assessments according to RECISTv1.1 criteria and it has not undergone surgery, radiology and/or other regional therapy (including but not limited to radiofrequency ablation, percutaneous ethanol injection, freezing therapy, high intensity focused ultrasound, transcatheter arterial chemoembolization, transcatheter arterial embolization). But if it progressed after the regional therapy, it could be selected as a target lesion. The local regional therapy must be done 4 weeks before randomization and the related AEs must recover to ≤ CTCAE grade 1.
- Child-Pugh score ≤7
- Eastern Cooperative Oncology Group (ECOG) 0 or 1
- Expected life time is over 12 weeks.
- HBV-DNA < 2000 IU/mL
- Organs function:
Platelet count ≥75×109/L Absolute neutrophil count (ANC) ≥1.5×109 /L White blood cell count ≥3.0×109 /L Haemoglobin ≥9.0 g/dL Serum total bilirubin ≤1.5×ULN ALT ≤5×ULN, and AST ≤5×ULN(ALT ≤3×ULN, and AST ≤3×ULN, if HCV-RNA is detectable) Albumin ≥28 g/L INR ≤1.5×ULN PT ≤1.5×ULN APTT ≤1.5×ULN Creatinine clearance (CL) >50 mL/min or serum creatinine ≤1.5×ULN Urine protein ≤1+ or ≤1.0g/24h 12. Patient is not fertile or willing and able to obey effective contraception.
Exclusion Criteria:
- Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC
- History of hepatic encephalopathy
- History of GI bleeding within 6 months, or investigator defined with high risk of haemorrhage for esophageal varices
- With distant metastasis (hilar lymph nodes metastasis is allowed)
- Co-infection of HBV and HCV
- History of other malignancy within 5 years except for healed local tumor.
- History of or plan to accept allogenic organ transplantation
- Ascites requiring invasive intervention (e.g. paracentesis) to maintain symptomatic control (every month or more often)
- History of myocardial infarction or unstable angina or uncontrolled arrythmia or stroke or cerebral hemorrhage within 6 months prior to randomization. QTcF value ≥450ms(male)or ≥470ms(female) detected by 12-lead electrocardiogram.
- New York Heart Association Grade ≥2 congestive heart failure or LVEF <50%
- Uncontrolled hypertension
- History of hypertensive crisis or hypertensive encephalopathy
- Active infection including but not limited to tuberculosis and HIV
- With interstitial lung disease, lung fibrosis, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia and serious impairment in lung function
- Active autoimmune disorders except patients with substitutional treatment with thyroid hormone and type I diabetes under treatment with insulin.
- Receipt of live attenuated vaccine within 28 days prior to randomization
- Current or prior use of steroids (>10mg/d prednisone) or immunosuppressive medication within 14 days before randomization
- Significant traumatic injury or major surgical procedure within 28 days prior to randomization
- Receipt of checkpoint inhibitors or T cell costimulatory drugs
- Receipt of bevacizumab or its analogues
- Involved in another clinical trial less than 14 days before randomization
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control
- Active bleeding, with history of ≥grade 3 bleeding within 6 months, or ≥grade 2 bleeding within 3 months
- Use of anti-thrombotics within 5 days prior to randomization
- In need of NSAIDs for long-term treatment.
- With one of the following diseases within 6 months before randomization:
(1) Digestive fistula, perforation and abscess (2) Gastrointestinal obstruction (3) Abdominal infection or inflammation (4) Major vascular disease 28. With severe and green wound, active ulcer or untreated fracture 29. History of drug abuse 30. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to screen for the study
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: HAIC + HLX10 + HLX04
HAIC: FOLFOX, q3w, up to 8 times; HLX10: 4.5mg/kg, iv, q3w, up to 2 years; HLX04: 15.0mg/kg, iv, q3w, up to 2 years.
|
For the HAIC procedure, a 5F catheter was introduced using the Seldinger technique through the femoral artery or the radial artery.
Then, angiographic surveys of the celiac trunk and superior mesenteric artery were performed.
According to tumor size, location, and arterial supply, the catheter or a 2.7F microcatheter was advanced into the hepatic artery at the level of selective segmental, lobar, or whole liver.
The catheter or microcatheter was connected to an external infusion pump.
The following regimen of modified FOLFOX was administered: oxaliplatin, 85mg/m2 for 2 hours; leucovorin, 400mg/m2; and 5-fluorouracil, 2400mg/m2 for 44-46 hours.
After HAIC treatment, the catheter or microcatheter, and the sheath were removed.
PD-1 antibody with proven efficacy in advanced hepatocellular carcinoma
Combination of PD-1 antibody and VEGF antibody might promote the efficacy of HAIC in hepatocellular carcinoma with major portal vein thrombosis.
|
Comparador de placebos: HAIC + Placebo
HAIC: FOLFOX, q3w, up to 8 times; Placebo1: saline, iv, q3w, up to 2 years; Placebo2: saline, iv, q3w, up to 2 years.
|
Placebo
For the HAIC procedure, a 5F catheter was introduced using the Seldinger technique through the femoral artery or the radial artery.
Then, angiographic surveys of the celiac trunk and superior mesenteric artery were performed.
According to tumor size, location, and arterial supply, the catheter or a 2.7F microcatheter was advanced into the hepatic artery at the level of selective segmental, lobar, or whole liver.
The catheter or microcatheter was connected to an external infusion pump.
The following regimen of modified FOLFOX was administered: oxaliplatin, 85mg/m2 for 2 hours; leucovorin, 400mg/m2; and 5-fluorouracil, 2400mg/m2 for 44-46 hours.
After HAIC treatment, the catheter or microcatheter, and the sheath were removed.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Objective response rate
Periodo de tiempo: The proportion of patients with complete response or partial response, through study completion, an average of 3 years.
|
efficacy
|
The proportion of patients with complete response or partial response, through study completion, an average of 3 years.
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Progression free survival
Periodo de tiempo: From date of randomization until the date of the first documented progression or date of death from any cause, whichever comes first, up to 48 months
|
efficacy
|
From date of randomization until the date of the first documented progression or date of death from any cause, whichever comes first, up to 48 months
|
Duration of response
Periodo de tiempo: From date of randomization until the date of first documented progression, up to 48 months
|
efficacy
|
From date of randomization until the date of first documented progression, up to 48 months
|
Time to response
Periodo de tiempo: From date of randomization until the date of first documented response, up to 48 months
|
efficacy
|
From date of randomization until the date of first documented response, up to 48 months
|
Time to progression
Periodo de tiempo: From date of randomization until the date of first documented progression, up to 48 months
|
efficacy
|
From date of randomization until the date of first documented progression, up to 48 months
|
Overall survival
Periodo de tiempo: From date of randomization until death from any cause, up to 48 months
|
efficacy
|
From date of randomization until death from any cause, up to 48 months
|
Progression free survival rate at 12-month time point
Periodo de tiempo: From date of randomization until 12-month time point
|
efficacy
|
From date of randomization until 12-month time point
|
Overall survival rate at 12-month time point
Periodo de tiempo: From date of randomization until 12-month time point
|
efficacy
|
From date of randomization until 12-month time point
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Objective response rate according to iRECIST criteria
Periodo de tiempo: The proportion of patients with complete response or partial response according to iRECIST criteria, through study completion, an average of 3 years.
|
efficacy
|
The proportion of patients with complete response or partial response according to iRECIST criteria, through study completion, an average of 3 years.
|
Progression free survival according to iRECIST criteria
Periodo de tiempo: From date of randomization until date of confirmed progression according to iRECIST criteria, up to 48 months
|
efficacy
|
From date of randomization until date of confirmed progression according to iRECIST criteria, up to 48 months
|
Duration of response according to iRECIST criteria
Periodo de tiempo: From date of randomization until date of confirmed progression according to iRECIST criteria, up to 48 months
|
efficacy
|
From date of randomization until date of confirmed progression according to iRECIST criteria, up to 48 months
|
Time to response according to iRECIST criteria
Periodo de tiempo: From date of randomization until date of the first documented response according to iRECIST criteria, up to 48 months
|
efficacy
|
From date of randomization until date of the first documented response according to iRECIST criteria, up to 48 months
|
Time to progression according to iRECIST criteria
Periodo de tiempo: From date of randomization until date of confirmed progression according to iRECIST criteria, up to 48 months.
|
efficacy
|
From date of randomization until date of confirmed progression according to iRECIST criteria, up to 48 months.
|
Adverse events rate
Periodo de tiempo: From date of randomization until 30 days after the last treatment or beginning of new anti-cancer therapy, whichever comes first, up to 48 months
|
Safety
|
From date of randomization until 30 days after the last treatment or beginning of new anti-cancer therapy, whichever comes first, up to 48 months
|
Severe adverse events rate
Periodo de tiempo: From date of randomization until 90 days after the last treatment, up to 48 months
|
Safety
|
From date of randomization until 90 days after the last treatment, up to 48 months
|
Discontinuation rate due to any adverse events
Periodo de tiempo: From date of randomization until the last treatment, up to 48 months
|
Safety
|
From date of randomization until the last treatment, up to 48 months
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Anticipado)
Finalización primaria (Anticipado)
Finalización del estudio (Anticipado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Digestivo
- Enfermedades cardiovasculares
- Enfermedades Vasculares
- Neoplasias por tipo histológico
- Neoplasias
- Neoplasias por sitio
- Adenocarcinoma
- Neoplasias Glandulares y Epiteliales
- Neoplasias del Sistema Digestivo
- Enfermedades del HIGADO
- Embolia y Trombosis
- Neoplasias Hepaticas
- Carcinoma
- Carcinoma Hepatocelular
- Trombosis
- Efectos fisiológicos de las drogas
- Factores inmunológicos
- Anticuerpos
- Inmunoglobulinas
Otros números de identificación del estudio
- HHH
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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. .