- ICH GCP
- Registre américain des essais cliniques
- Essai clinique 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
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
-
-
Florida
-
Tampa, Florida, États-Unis, 33612
- H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
-
-
New York
-
New York, New York, États-Unis, 10467
- Montefiore Medical Center
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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 d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: 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. |
Autres noms:
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
---|---|
Nombre de patients présentant des événements indésirables après un traitement par Melphalan/HDS.
Délai: 2 années
|
2 années
|
Number of patients with adverse events after treatment with Sorafenib following treatment with Melphalan/HDS.
Délai: 2 years
|
2 years
|
Taux de réponse objective en pourcentage du traitement Melphalan/HDS
Délai: 2 années
|
2 années
|
Progression free survival in months of patients receiving Melphalan/HDS treatment followed by Sorafenib
Délai: 2 years
|
2 years
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
AUC of melphalan after Melphalan/HDS treatment
Délai: 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
Délai: 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.
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Directeur d'études: Leslie Callahan, RN, Delcath Systems
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système digestif
- Tumeurs par type histologique
- Tumeurs
- Tumeurs par site
- Adénocarcinome
- Tumeurs, glandulaires et épithéliales
- Tumeurs du système digestif
- Maladies du foie
- Tumeurs du foie
- Carcinome
- Carcinome hépatocellulaire
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Inhibiteurs d'enzymes
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Agents antinéoplasiques, alkylants
- Agents d'alkylation
- Agonistes myéloablatifs
- Inhibiteurs de protéine kinase
- Sorafénib
- Melphalan
Autres numéros d'identification d'étude
- PHP-HCC-201
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
Essais cliniques sur Carcinome hépatocellulaire (CHC)
-
Qianfoshan HospitalPas encore de recrutement
-
University of PisaAzienda Ospedaliera Città della Salute e della Scienza di Torino; Fondazione... et autres collaborateursRecrutement
-
Seoul National University HospitalPhilips HealthcareComplété
-
Huazhong University of Science and TechnologyInconnue
-
Taipei Medical University WanFang HospitalRésilié
-
Qianfoshan HospitalPas encore de recrutement
-
Xuhua DuanRecrutement
-
Chen XiaopingPas encore de recrutement
-
Henan Cancer HospitalPas encore de recrutement
Essais cliniques sur Sorafénib
-
BayerComplétéCarcinome hépatocellulaireTaïwan
-
Cancer Institute and Hospital, Chinese Academy...ComplétéCarcinome hépatocellulaire, radiothérapie, sorafenibChine
-
Xspray Pharma ABComplétéPharmacocinétique | BiodisponibilitéRoyaume-Uni
-
Yamagata UniversityInconnueCarcinome rénal métastatiqueJapon
-
Institute of Liver and Biliary Sciences, IndiaComplétéCarcinome hépatocellulaireInde
-
BayerComplétéCarcinome à cellules rénales | Carcinome à cellules rénales (avancé)Pologne, Chine, Slovaquie, France, Allemagne, Indonésie, Corée, République de, Suède, Philippines, L'Autriche, Colombie, République tchèque, Mexique, Fédération Russe, Slovénie, Argentine, Grèce, Pays-Bas
-
BayerComplétéCarcinome à cellules rénalesJapon
-
BayerComplété
-
BayerComplétéCarcinome hépatocellulaireBelgique, France, Espagne, Chine, Hong Kong, États-Unis, Canada, Suisse, Allemagne, Le Portugal, Taïwan, Japon, Fédération Russe, Singapour, L'Autriche, Royaume-Uni, Corée, République de, Australie, Nouvelle-Zélande, Mexique, Brésil et plus
-
Sun Yat-sen UniversityComplétéCancer du foie | Carcinome hépatiqueChine