A Randomized, Controlled Study to Compare the Efficacy, Safety and Pharmacokinetics of Melphalan/HDS Treatment Given SequentiallyFollowing Cisplatin/Gemcitabine versus Cisplatin/Gemcitabine (Standard of Care) in Patients with cancer of the bile ducts in the liver
- Conditions
- Intrahepatic cholangiocarcinomaMedDRA version: 20.0Level: LLTClassification code 10073077Term: Intrahepatic cholangiocarcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003812-10-IT
- Lead Sponsor
- DELCATH SYSTEMS, INCORPORATIONS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 246
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
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 <30 days prior to first treatment.
8. Prior radiation therapy to liver including 90Y-, I131-based locoregional therapy. Prior loco-regional therapy, inc. resection, based on other technology for ICC, must have completed >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 <100,000/µL
b. Hemoglobin <10.0g/dL, independent of transfusion or growth factor support
c. White blood cell count <2,000/µL
d. Neutrophils <1,500cells/µL.
20. Serum creatinine >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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method