An International Multi-center Phase 2 Study to Evaluate the Efficacy and Safety of Melphalan/HDS Treatment in Patients with Unresectable Hepatocellular Carcinoma or Intra hepatic Cholangiocarcinoma.
- Conditions
- unresectable hepatocellular carcinoma (HCC) confined to the liver and Intra hepatic Cholangiocarcinoma confined to the liver.MedDRA version: 18.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864MedDRA version: 18.1Level: LLTClassification code 10073077Term: Intrahepatic cholangiocarcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-001585-98-DE
- Lead Sponsor
- Delcath Systems, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 42
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:
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
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, hepatic vasculature incompatible with perfusion, hepatofugal flow in the portal vein or known unresolved venous shunting. Prior Whipple procedure is permitted provided the anatomy is still compatible for perfusion with the Melphalan/HDS system.
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 enrollme
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 Delivery System (HDS) treatment in patients with unresectable hepatocellular carcinoma (HCC) or intra-hepatic cholangiocarcinoma (ICC) confined to the liver.;Secondary Objective: Secondary<br>• To evaluate the safety of melphalan administered by Melphalan/Hepatic Delivery System (HDS)<br>• To assess the progression free survival (PFS) of patients receiving Melphalan/Hepatic Delivery System (HDS)<br><br>Exploratory<br>• To characterize the systemic exposure of melphalan administered by 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 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 Melphalan/HDS<br>•To characterize the systemic exposure of melphalan administered by 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 the last Melphalan/HDS treatment. Ongoing AEs at the end-of-treatment visit will be followed until the severity returns to baseline or CTCAE Grade = 1. All patients will be followed for disease status and chronic toxicity up to 2 years after the last dose of study treatment until death, consent withdrawal or the patient is lost to follow-up, whichever occurs the earliest.