An International Multi-center Phase 2 Study to Evaluate the Efficacy andSafety of Melphalan/HDS Treatment in Patients with UnresectableHepatocellular Carcinoma or Intra hepatic Cholangiocarcinoma.

Phase 1

Conditions: nresectable hepatocellular carcinoma (HCC) confined to the liver andIntra hepatic Cholangiocarcinoma confined to the liver.
MedDRA version: 20.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864
MedDRA version: 20.0Level: LLTClassification code 10073077Term: Intrahepatic cholangiocarcinomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-001585-98-IT

Lead Sponsor: DELCATH SYSTEMS, INCORPORATIONS

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 42

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 extra-hepatic disease
(minor lesions [= 1 cm and not consistent with metastatic disease]
acceptable) based on computed tomography (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. Child-Pugh Class A.
5. ECOG PS 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 or imaging study.
2. Unresectable ICC without clinically significant extra-hepatic disease
(minor lesions [= 1 cm and not consistent with metastatic disease]
acceptable) 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. Child-Pugh Class A.
5. ECOG PS 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 ICC, if any, must have been completed at
least 4 weeks prior to baseline imaging.
7. Age = 18 years.
8. Signed informed consent
Are the trial subjects under 18? no
Number of subjects for this age range: 1
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

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, for both the HCC and ICC cohorts, 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 [NCI] CTCAE version 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 and Hepatitis C infection.
Patients with anti-hepatitis B core antigen (HBc) positive, or hepatitis B
surface antigen (HBsAg) but viral deoxyribonucleic acid (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 < 90,000/µL
b. Hemoglobin < 8 g/dL, independent of transfusion or growth factor
support
c. Neutrophils < 1,500 cells/µL.
18. Serum creatinine > 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 (PT)/international normalized ratio (INR) > 1.5
c. Aspartate aminotransferase (AST) > 10 times the upper limit of
normal (ULN) or alanine aminotransferase (ALT) > 5 times ULN
d. Serum albumin < 3.0 g/dL.
20. Known alcohol abuse.
21. For female subjects of childbearing potential (i.e., have had a
menstrual period within the past 12 months): a positive serum
pregnancy test (ß-human chorionic gonadotropin [ß-HCG]) within 7 days
prior to enrollment; or unwilling or unable to undergo hormonal
suppression to avoid menstruation during treatment.
22. Sexually active females of childbearing potential and sexually active

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To estimate the objective response rate (ORR) of Melphalan/Hepatic<br>Delivery System (HDS) treatment in patients with unresectable<br>hepatocellular carcinoma (HCC) or intra-hepatic cholangiocarcinoma<br>(ICC) confined to the liver.;Secondary Objective: • To evaluate the safety of melphalan administered by<br>Melphalan/Hepatic Delivery System (HDS)<br>• To assess the progression free survival (PFS) of patients receiving Melphalan/Hepatic Delivery System (HDS).<br>Exploratory:<br>• To characterize the systemic exposure of melphalan administered by<br>Melphalan/Hepatic Delivery System (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<br>Melphalan/HDS treatment.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • To evaluate the safety of melphalan administered by Melphalan/HDS<br>• To assess the progression free survival of patients receiving<br>Melphalan/HDS<br>•To characterize the systemic exposure of melphalan administered by<br>Melphalan/HDS at selected study sites;Timepoint(s) of evaluation of this end point: Patients will have the end-of-treatment visit in 6 to 8 weeks following<br>the last Melphalan/HDS treatment. Ongoing AEs at the end-of-treatment<br>visit will be followed until the severity returns to baseline or CTCAE<br>Grade = 1. All patients will be followed for disease status and chronic<br>toxicity up to 2 years after the last dose of study treatment until death,<br>consent withdrawal or the patient is lost to follow-up, whichever occurs<br>the earliest.

Related Trials