- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT02406508
Sequential Melphalan for Use With Hepatic Delivery System Treatment Followed by Sorafenib in Patients With Unresectable HCC
An International Multi-center Phase 2 Study to Evaluate the Safety and Efficacy of Sequential Melphalan Hydrochloride for Injection for Use With the Hepatic Delivery System Treatment Followed by Sorafenib in Patients With Unresectable Hepatocellular Carcinoma
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This is a single arm, open label, multi-center, phase 2 study to evaluate the safety and efficacy of sequential treatment with Melphalan/HDS followed by sorafenib in patients with unresectable hepatocellular carcinoma (HCC) confined to the liver.
Eligible patients will receive up to 3 Melphalan/HDS treatments. Each treatment cycle consists of 6 weeks with an acceptable delay for another 2 weeks before next planned treatment. The Melphalan/HDS treatment will be terminated in patients with progressive disease (PD), complete response (CR), and > 8 weeks delay of recovery from toxicity after last PHP treatment.
With the exception of patients with PD, all patients will be treated with sorafenib after completing the Melphalan/HDS treatment. Patients with PD will be managed with standard of care off-study by their treating physician.
Tipo de estudio
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Florida
-
Tampa, Florida, Estados Unidos, 33612
- H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
-
-
New York
-
New York, New York, Estados Unidos, 10467
- Montefiore Medical Center
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- HCC diagnosed by tissue or imaging study
- Unresectable HCC without extrahepatic disease based on CT
- At least one target lesion. In patients with prior loco-regional therapy, the target lesion(s) must be located in area(s) outside previous treatment
- Child-Pugh Class A in the absence of hepatoencephalopathy or clinically evident ascites
- Barcelona Clinic Liver Cancer (BCLC) stage B
- MELD Score < 15
- Eastern Cooperative Oncology Group Performance Status 0-1
- No prior systemic therapy for HCC
- No prior radiation therapy to the liver including Y90-, I131-based loco-regional therapy. Prior loco-regional therapy based on other technology for HCC, if any, must have been completed at least 4 weeks prior to baseline imaging
- Age ≥ 18 years
- Signed informed consent
Exclusion Criteria:
- Metastatic disease outside of liver
- Greater than 50% tumor burden in the liver by imaging
- History of orthotopic liver transplantation, clinical symptoms of portal hypertension, Whipple's procedure, hepatic artery anatomy incompatible with perfusion or known unresolved venous shunting
- Evidence of ascites on imaging study, or the use of diuretics for ascites
- Clinically significant encephalopathy
- History of allergies or known hypersensitivity to any components of melphalan or the components of the Melphalan/HDS system
- Known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia
- Received an investigational agent for any indication within 30 days prior to first treatment
- Not recovered from side effects of prior therapy to ≤ grade 1 (according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [NCI CTCAE v. 4.03]). Certain side effects that are unlikely to develop into serious or life-threatening events (e.g. alopecia) are allowed at > grade 1
- Those with New York Heart Association functional classification II, III or IV; active cardiac conditions including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia
- History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia
- Uncontrolled diabetes mellitus, hypothyroidism, or hyperthyroidism
- Active uncontrolled infection, including Hepatitis B, Hepatitis C infection. Patients with anti-HBc positive, or HBsAg but DNA negative are exception(s)
- History of bleeding disorders
- Brain lesions with a propensity to bleed
- Known esophageal varices at risk of bleeding, including medium or large esophageal or gastric varices, or active peptic ulcer
- Previous malignancy within 3 years prior to enrollment, except for curatively-treated basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, bladder carcinoma in situ or breast cancer in situ
Inadequate hematologic function as evidenced by any of the following:
- Platelets < 125,000/µL
- Hemoglobin ≤ 10 g/dL, independent of transfusion or growth factor support
- Neutrophils < 1,500/µL
- Serum creatinine > 1.5 mg/dL
Inadequate liver function as evidenced by any of the following:
- Total serum bilirubin ≥ 2.0 mg/dL
- Prothrombin time International Normalized Ratio (INR) > 1.5
- Aspartate aminotransferase (AST) or alanine transaminase (ALT) > 5 times ULN
- Serum albumin < 3.0 g/dL
- Alcohol consumption within 30 days of first study treatment, or refusing to abstain from alcohol for the duration of study treatment
- For female subjects of childbearing potential (i.e., have had a menstrual period within the past 12 months): a positive serum pregnancy test (β-human chorionic gonadotropin) within 7 days prior to enrollment; or unwilling or unable to undergo hormonal suppression to avoid menstruation during treatment
- Sexually active females of childbearing potential and sexually active males with partners of reproductive potential: unwilling or unable to use appropriate contraception from screening until at least 30 days after last administration of study treatment
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: Hepatic Delivery System Treatment followed by Sorafenib
Percutaneous hepatic perfusion with melphalan hydrochloride for injection using the Hepatic Delivery System. Melphalan hydrochloride is administered at a dose of 3mg/kg ideal body weight once every 6 weeks for a maximum of 3 cycles of treatment. After the Melphalan/HDS treatment patients will be treated with sorafenib according to the package prescribing information. |
Otros nombres:
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
---|---|
Número de pacientes con eventos adversos tras el tratamiento con Melfalán/HDS.
Periodo de tiempo: 2 años
|
2 años
|
Number of patients with adverse events after treatment with Sorafenib following treatment with Melphalan/HDS.
Periodo de tiempo: 2 years
|
2 years
|
Tasa de respuesta objetiva en porcentaje de tratamiento con Melfalán/HDS
Periodo de tiempo: 2 años
|
2 años
|
Progression free survival in months of patients receiving Melphalan/HDS treatment followed by Sorafenib
Periodo de tiempo: 2 years
|
2 years
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
AUC of melphalan after Melphalan/HDS treatment
Periodo de tiempo: Baseline - prior to infusion. Infusion period - 10 min, 20 min, End of infusion. Washout period - 10 min, 20 min, 30 min. Post-procedure period - 5 min, 10 min, 15 min, 30 min, 1 hour, 2 hours, 3.5 hours, 5 hours.
|
Pharmacokinetic study
|
Baseline - prior to infusion. Infusion period - 10 min, 20 min, End of infusion. Washout period - 10 min, 20 min, 30 min. Post-procedure period - 5 min, 10 min, 15 min, 30 min, 1 hour, 2 hours, 3.5 hours, 5 hours.
|
Quality of life questionnaires
Periodo de tiempo: Baseline, Week 6 of each PHP cycle, Day 1 of every Sorafenib cycle, End of treatment, every 12 weeks in follow-up.
|
Baseline, Week 6 of each PHP cycle, Day 1 of every Sorafenib cycle, End of treatment, every 12 weeks in follow-up.
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Leslie Callahan, RN, Delcath Systems
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
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
- Neoplasias por tipo histológico
- Neoplasias
- Neoplasias por sitio
- Adenocarcinoma
- Neoplasias Glandulares y Epiteliales
- Neoplasias del Sistema Digestivo
- Enfermedades del HIGADO
- Neoplasias Hepaticas
- Carcinoma
- Carcinoma Hepatocelular
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes antineoplásicos, alquilantes
- Agentes alquilantes
- Agonistas mieloablativos
- Inhibidores de la proteína quinasa
- Sorafenib
- Melfalán
Otros números de identificación del estudio
- PHP-HCC-201
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. .
Ensayos clínicos sobre Carcinoma hepatocelular (CHC)
-
Seoul National University HospitalBayerTerminadoDiagnóstico | HccCorea, república de
-
Academisch Medisch Centrum - Universiteit van Amsterdam...Erasmus Medical CenterTerminadoBCLC etapa C HCC | Cirrosis hepática CP-BPaíses Bajos
-
Beijing Tsinghua Chang Gung HospitalDesconocidoCarcinoma hepatocelular enorme (HCC) (≥10 cm)Porcelana
-
Ain Shams UniversityTerminado
-
Qing XIeReclutamientoHepatitis B crónica | Riesgo intermedio a alto de HCCPorcelana
Ensayos clínicos sobre Sorafenib
-
BayerAmgenTerminado
-
Technical University of MunichTerminadoCarcinoma de células renalesAustria, Alemania, Países Bajos
-
Ottawa Hospital Research InstituteBayerTerminadoCáncer colorrectal metastásicoCanadá
-
Ohio State University Comprehensive Cancer CenterBayerTerminado
-
British Columbia Cancer AgencyRetiradoCarcinomas de células escamosas de cabeza y cuello localmente avanzados (SCCHN)Canadá
-
Yiviva Inc.ReclutamientoCarcinoma hepatocelular avanzadoEstados Unidos, Taiwán, Porcelana, Hong Kong
-
BayerTerminadoCarcinoma hepatocelularTaiwán
-
New Mexico Cancer Care AllianceTerminadoCarcinoma metastásico de células renalesEstados Unidos
-
Cancer Institute and Hospital, Chinese Academy...TerminadoCarcinoma Hepatocelular, Radioterapia, SorafenibPorcelana
-
Xspray Pharma ABTerminadoFarmacocinética | BiodisponibilidadReino Unido