Sequential Melphalan for Use With Hepatic Delivery System Treatment Followed by Sorafenib in Patients With Unresectable HCC

NCT02406508 | Withdrawn Phase 2 DMC

• 1 other identifier: PHP-HCC-201
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single arm, open label, multi-center, phase 2 study to evaluate the safety and efficacy of sequential treatment with Melphalan/HDS followed by sorafenib in patients with unresectable hepatocellular carcinoma (HCC) confined to the liver.

Conditions

Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (4)

• Number of patients with adverse events after treatment with Melphalan/HDS.

  2 years

• Number of patients with adverse events after treatment with Sorafenib following treatment with Melphalan/HDS.

  2 years

• Objective response rate in percentage of Melphalan/HDS treatment

  2 years

• Progression free survival in months of patients receiving Melphalan/HDS treatment followed by Sorafenib

  2 years

Other Outcomes (2)

• AUC of melphalan after Melphalan/HDS treatment

  Baseline - prior to infusion. Infusion period - 10 min, 20 min, End of infusion. Washout period - 10 min, 20 min, 30 min. Post-procedure period - 5 min, 10 min, 15 min, 30 min, 1 hour, 2 hours, 3.5 hours, 5 hours.

• Quality of life questionnaires

  Baseline, Week 6 of each PHP cycle, Day 1 of every Sorafenib cycle, End of treatment, every 12 weeks in follow-up.

Study Arms (1)

Hepatic Delivery System Treatment followed by Sorafenib

EXPERIMENTAL

Percutaneous hepatic perfusion with melphalan hydrochloride for injection using the Hepatic Delivery System. Melphalan hydrochloride is administered at a dose of 3mg/kg ideal body weight once every 6 weeks for a maximum of 3 cycles of treatment. After the Melphalan/HDS treatment patients will be treated with sorafenib according to the package prescribing information.

Device: Melphalan/HDS; Drug: Sorafenib

Interventions

Melphalan/HDS DEVICE

Also known as: Melphalan/Hepatic Delivery System, Percutaneous hepatic perfusion (PHP)

Hepatic Delivery System Treatment followed by Sorafenib

Sorafenib DRUG

Also known as: Nexavar

Hepatic Delivery System Treatment followed by Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HCC diagnosed by tissue or imaging study
• Unresectable HCC without extrahepatic disease based on CT
• At least one target lesion. In patients with prior loco-regional therapy, the target lesion(s) must be located in area(s) outside previous treatment
• Child-Pugh Class A in the absence of hepatoencephalopathy or clinically evident ascites
• Barcelona Clinic Liver Cancer (BCLC) stage B
• MELD Score \< 15
• Eastern Cooperative Oncology Group Performance Status 0-1
• No prior systemic therapy for HCC
• No prior radiation therapy to the liver including Y90-, I131-based loco-regional therapy. Prior loco-regional therapy based on other technology for HCC, if any, must have been completed at least 4 weeks prior to baseline imaging
• Age ≥ 18 years
• Signed informed consent

You may not qualify if:

• Metastatic disease outside of liver
• Greater than 50% tumor burden in the liver by imaging
• History of orthotopic liver transplantation, clinical symptoms of portal hypertension, Whipple's procedure, hepatic artery anatomy incompatible with perfusion or known unresolved venous shunting
• Evidence of ascites on imaging study, or the use of diuretics for ascites
• Clinically significant encephalopathy
• History of allergies or known hypersensitivity to any components of melphalan or the components of the Melphalan/HDS system
• Known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia
• Received an investigational agent for any indication within 30 days prior to first treatment
• 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
• 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
• History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia
• Uncontrolled diabetes mellitus, hypothyroidism, or hyperthyroidism
• Active uncontrolled infection, including Hepatitis B, Hepatitis C infection. Patients with anti-HBc positive, or HBsAg but DNA negative are exception(s)
• History of bleeding disorders
• Brain lesions with a propensity to bleed

Sponsors & Collaborators

• Delcath Systems Inc.: lead

Study Sites (2)

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, 33612, United States

Location

Montefiore Medical Center

New York, New York, 10467, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Leslie Callahan, RN

  Delcath Systems

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2015
• First Posted: April 2, 2015
• Study Start: October 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: December 18, 2017

Record last verified: 2017-12

Locations

US (2)