unresectable hepatocellular carcinoma (HCC) confined to the liver and Intra hepatic Cholangiocarcinoma confined to the liver MedDRA version: 17.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 100000004864 MedDRA version: 17.1 Level: LLT Classification code 10073077 Term: Intra
Conditions
Interventions
Product Name: Melphalan
Pharmaceutical Form: Powder for injection
INN or Proposed INN: MELPHALAN
CAS Number: 3223-07-2
Other descriptive
Sponsors
Delcath Systems, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with HCC must meet all of the following criteria for study entry: 1. HCC diagnosed by tissue or imaging study 2. Unresectable HCC without clinically significant extrahepatic disease based on CT 3. At least one target lesion based on mRECIST for HCC. In patients with prior loco-regional therapy, the target lesion(s) must be located in area(s) outside previous treatment or having progressed after prior treatment if located within previous treatment field. 4. Child-Pugh Class A 5. Eastern Cooperative Oncology Group Performance Status 0-1 6. No prior radiation therapy to the liver including Y90-, I131-based loco-regional therapy. Prior loco-regional therapy, including resection, based on other technology for HCC, if any, must have been completed at least 4 weeks prior to baseline imaging 7. Age = 18 years 8. Signed informed consent Patients with ICC must meet all of the following criteria for study entry: 1. ICC diagnosed by tissue biopsy and imaging study 2. Unresectable ICC without clinically significant extra hepatic disease based on CT 3. At least one target lesion based on mRECIST. In patients with prior loco regional therapy, the target lesion(s) must be located in area(s) outside previous treatment or must have progressed after prior treatment if located within previous treatment field. 4. ECOG PS 0-1 5. No prior radiation therapy to the liver including Y90 , I131 based loco regional therapy. Prior loco regional therapy, including resection, based on other technology for ICC, if any, must have been completed at least 4 weeks prior to baseline imaging 6. Age = 18 years 7. Signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 21 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 21
Exclusion criteria
Exclusion criteria: For the HCC cohort, patients for whom transplantation, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), or systemic treatment with sorafenib are better therapeutic options are to be excluded from study entry. Additionally, patients who meet any of the following criteria will be excluded from study entry: 1. Greater than 50% tumor burden in the liver by imaging 2. History of orthotopic liver transplantation, Whipple’s procedure, hepatic vasculature incompatible with perfusion, hepatofugal flow in the portal vein or known unresolved venous shunting 3. Evidence of ascites on imaging study, or the use of diuretics for ascites 4. Clinically significant encephalopathy 5. History of, or known, hypersensitivity to any components of melphalan or the components of the Melphalan/HDS system 6. Known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia 7. Received an investigational agent for any indication within 30 days prior to first treatment 8. 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 9. 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 10. History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia 11. Uncontrolled diabetes mellitus, hypothyroidism, or hyperthyroidism 12. Active infection, including Hepatitis B, Hepatitis C infection. Patients with anti-HBc positive, or HBsAg but DNA negative are exception(s) 13. History of bleeding disorders 14. Brain lesions with a propensity to bleed 15. Known varices at risk of bleeding, including medium or large esophageal or gastric varices, or active peptic ulcer 16. 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 17. Inadequate hematologic function as evidenced by any of the following: a. Platelets 1.5 mg/dL 19. Inadequate liver function as evidenced by any of the following: a. Total serum bilirubin = 2.0 mg/dL b. Prothrombin time International Normalized Ratio (INR) > 1.5 c. Aspartate aminotransferase (AST) > 10 times ULN or alanine transaminase (ALT) > 5 times ULN d. Serum albumin < 3.0 g/dL Patients with ICC must meet the followin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the objective response rate of Melphalan/HDS treatment in patients with unresectable HCC or intra hepatic cholangiocarcinoma (ICC) confined in the liver. ; Secondary Objective: Secondary • To evaluate the safety of melphalan administered by Melphalan/HDS • To assess the progression free survival of patients receiving Melphalan/HDS Exploratory • To characterize the systemic exposure of melphalan administered by Melphalan/HDS at selected study sites ;Primary end point(s): objective response rate of Melphalan/HDS treatment ;Timepoint(s) of evaluation of this end point: The study endpoint will be measured at the conclusion of Melphalan/HDS treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To evaluate the safety of melphalan administered by Melphalan/HDS • To assess the progression free survival of patients receiving Melphalan/HDS •To characterize the systemic exposure of melphalan administered by Melphalan/HDS at selected study sites ; Timepoint(s) of evaluation of this end point: Safety will be assessed on an ongoing basis. Patients will be followed for safety from study entry until at least 30 days from their last study treatment. Chronic toxicity, if any, will be followed for one year after last dose, until death, withdrawal of informed consent or lost to follow-up, whichever occurs earliest. Time points for the endpoint outcome measurements are detailed in section 5.6 and schedule of events in the protocol. | — |
Countries
Germany, Italy, Netherlands, United Kingdom, United States
Contacts
Public ContactClinical Trials Desk
Delcath Systems, Inc
Outcome results
None listed