Intrahepatic cholangiocarcinoma MedDRA version: 20.0 Level: LLT Classification code 10073077 Term: Intrahepatic cholangiocarcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Melphalan hydrochloride solution for injection
Product Name: Melphalan hydrochloride for injection
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: MELFALAN
Sponsors
DELCATH SYSTEMS, INCORPORATIONS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Are willing and able to provide signed informed consent. 2. Intrahepatic cholangiocarcinoma diagnosed by histology. 3. Unresectable ICC, with less than 50% of the liver involved, and without clinically significant extra-hepatic disease (regional lymph node lesions [= 2 cm] are acceptable) based on CT. Scans used to determine eligibility (CT scan of the chest/abdomen/pelvis and liver) must be performed within 28 days prior to initiation of Induction Phase treatment. 4. At least one target lesion based on the evaluation criteria in solid tumors (RECIST 1.1). 5. Patients must have an ECOG PS of 0-1 at screening. 6. Male or female patients aged = 18 years. 7. Patients must weigh = 35 kg (due to possible size limitations with respect to percutaneous catheterization of the femoral artery and vein using the Delcath Hepatic Delivery System). 8. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (ß-human chorionic gonadotropin) within 7 days prior to induction treatment. 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 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 136
Exclusion criteria
Exclusion criteria: 1. >50% tumor burden in the liver by imaging. 2. History of orthotopic liver transplantation, hepatic vasculature incompatible with perfusion, hepatofugal flow in the portal vein or known unresolved venous shunting. Prior Whipple procedure permitted provided anatomy is still compatible for perfusion with Melphalan/HDS system. 3. History of/known hypersensitivity to any components of melphalan or components of Melphalan/HDS system. 4. History of/known hypersensitivity to gemcitabine or platinumcontaining compounds. 5. Known hypersensitivity to heparin/presence of heparin-induced thrombocytopenia. 6. Prior treatment with gemcitabine/platinum-containing compounds, including in adjuvant setting. 7. Received investigational agent for any indication 4 weeks prior to baseline imaging. 9. Not recovered from side effects of prior therapy to =Grade 1. Certain side effects unlikely to develop into serious/life–threatening events allowed >Grade 1. 10. Those with NYHA functional classification II, III or IV; active cardiac conditions inc. unstable coronary syndromes (unstable/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. 11. History/evidence of clinically significant pulmonary disease that precludes use of general anesthesia. 12. Any evidence of severe/uncontrolled systemic diseases which, in view of investigator, make it undesirable for patient to participate in the trial. 13. Patients with active bacterial infections with systemic manifestations (malaise, fever, leukocytosis) not eligible until completion of appropriate therapy except patients taking low-dose antibiotics for biliary obstruction. 14. History of prior malignancy that will interfere with responseevaluation (exceptions include in-situ carcinoma of cervix treated by cone-biopsy/resection, non-metastatic basal and/or squamous cell carcinomas of the skin, any early stage (stage I) malignancy adequately resected for cure >5 years previously). 15. Acute or active hepatitis B or hepatitis C infection. Patients with anti-HBc antigen positive, or HBsAg but viral DNA negative are exception(s). 16. History of bleeding disorders which would put patient at risk for bleeding with anti-coagulation or patients with increased risk of thromboembolic or hemorrhagic events. 17. Brain lesions or intracranial abnormalities at risk for bleeding by history or radiologic imaging. 18. Known varices at risk of bleeding, inc. medium/large esophageal orgastric varices/active peptic ulcer. 19. Inadequate hematologic function as evidenced by any of the following: a. Platelets 1.5mg/dL. If serum creatinine >1.5mg/dL, measured creatinine clearance must be measured and patient is eligible if creatinine clearance >45mL/min. 21. Inadequate liver function as evidenced by any of the following: a. Total serum bilirubin >1.5 times ULN b. Aspartate aminotransferase >5 times the upper limit of normal or alanine aminotransferase >5 times ULN c. Serum albumin <2.9g/dL. 22. K
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the overall survival (OS) in patients with intrahepatic cholangiocarcinoma treated with Melphalan/HDS given sequentially following cisplatin/gemcitabine versus cisplatin/gemcitabine.;Secondary Objective: ¿ To compare the overall progression-free survival in patients with intrahepatic cholangiocarcinoma treated with Melphalan/HDS given sequentially following cisplatin/gemcitabine versus cisplatin/gemcitabine, as determined by Independent Review Committee (IRC). The PFS will be evaluated at 110 PFS events to determine a "go/no go" decision. ¿ To compare the objective response rate (ORR = complete response [CR] + partial response [PR]), as determined by the Investigator ¿ To evaluate the safety of Melphalan/HDS treatment given sequentially following cisplatin/gemcitabine in patients with intrahepatic cholangiocarcinoma. ;Primary end point(s): The primary efficacy endpoint for this study is overall Survival and is defined as the time from date of randomization to date of death. In the absence of confirmation of death, survival time will be censored at the last date of follow-up when the patient was known to be alive (i.e. date reported for study medication, adverse event, vital sign, concomitant medication, phone contact, etc.).;Timepoint(s) of evaluation of this end point: Overall Survival (OS) at 190 OS events. The study will continue until survival follow-up is complete in all enrolled patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-free survival as determined by Independent Review Committee (IRC) is defined as the time from the date of randomization to first objective documentation of tumor progression (irrespective of initiation of a new or different systemic treatment) or to death due to any cause. 2. Objective Response Rate (ORR = CR + PR) as determined by the Investigator is a binary variable identifying whether or not the patient achieved a best overall (hepatic and extra-hepatic) response of PR or CR using RECIST 1.1 criteria.;Timepoint(s) of evaluation of this end point: 1. Progression Free Survival (PFS) interim analysis at 110 PFS events; ¿ Only if Progression Free Survival is statistically significant at the prespecified level (p<0.20, two-sided) will the study continue to enrolment of patients for the confirmatory endpoint of overall survival. 2. Progression Free Survival at the time final overall survival analysis takes place 3. Objective Response Rate (ORR) at the time final overall survival analysis takes place | — |
Countries
Germany, Italy, United States
Contacts
Public ContactClinical Operations
Delcath Systems Inc.
Outcome results
None listed