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

NCT ID: NCT02406508

Last Updated: 2017-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-31

Study Completion Date

2017-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Eligible patients will receive up to 3 Melphalan/HDS treatments. Each treatment cycle consists of 6 weeks with an acceptable delay for another 2 weeks before next planned treatment. The Melphalan/HDS treatment will be terminated in patients with progressive disease (PD), complete response (CR), and \> 8 weeks delay of recovery from toxicity after last PHP treatment.

With the exception of patients with PD, all patients will be treated with sorafenib after completing the Melphalan/HDS treatment. Patients with PD will be managed with standard of care off-study by their treating physician.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hepatocellular Carcinoma (HCC)

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Hepatic Delivery System Treatment followed by Sorafenib

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.

Group Type EXPERIMENTAL

Melphalan/HDS

Intervention Type DEVICE

Sorafenib

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Melphalan/HDS

Intervention Type DEVICE

Sorafenib

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Melphalan/Hepatic Delivery System Percutaneous hepatic perfusion (PHP) Nexavar

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. HCC diagnosed by tissue or imaging study
2. Unresectable HCC without extrahepatic disease based on CT
3. 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
4. Child-Pugh Class A in the absence of hepatoencephalopathy or clinically evident ascites
5. Barcelona Clinic Liver Cancer (BCLC) stage B
6. MELD Score \< 15
7. Eastern Cooperative Oncology Group Performance Status 0-1
8. No prior systemic therapy for HCC
9. 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
10. Age ≥ 18 years
11. Signed informed consent

Exclusion Criteria

1. Metastatic disease outside of liver
2. Greater than 50% tumor burden in the liver by imaging
3. History of orthotopic liver transplantation, clinical symptoms of portal hypertension, Whipple's procedure, hepatic artery anatomy incompatible with perfusion or known unresolved venous shunting
4. Evidence of ascites on imaging study, or the use of diuretics for ascites
5. Clinically significant encephalopathy
6. History of allergies or known hypersensitivity to any components of melphalan or the components of the Melphalan/HDS system
7. Known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia
8. Received an investigational agent for any indication within 30 days prior to first treatment
9. 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
10. 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
11. History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia
12. Uncontrolled diabetes mellitus, hypothyroidism, or hyperthyroidism
13. Active uncontrolled infection, including Hepatitis B, Hepatitis C infection. Patients with anti-HBc positive, or HBsAg but DNA negative are exception(s)
14. History of bleeding disorders
15. Brain lesions with a propensity to bleed
16. Known esophageal varices at risk of bleeding, including medium or large esophageal or gastric varices, or active peptic ulcer
17. 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
18. Inadequate hematologic function as evidenced by any of the following:

* Platelets \< 125,000/µL
* Hemoglobin ≤ 10 g/dL, independent of transfusion or growth factor support
* Neutrophils \< 1,500/µL
19. Serum creatinine \> 1.5 mg/dL
20. Inadequate liver function as evidenced by any of the following:

* Total serum bilirubin ≥ 2.0 mg/dL
* Prothrombin time International Normalized Ratio (INR) \> 1.5
* Aspartate aminotransferase (AST) or alanine transaminase (ALT) \> 5 times ULN
* Serum albumin \< 3.0 g/dL
21. Alcohol consumption within 30 days of first study treatment, or refusing to abstain from alcohol for the duration of study treatment
22. For female subjects of childbearing potential (i.e., have had a menstrual period within the past 12 months): a positive serum pregnancy test (β-human chorionic gonadotropin) within 7 days prior to enrollment; or unwilling or unable to undergo hormonal suppression to avoid menstruation during treatment
23. Sexually active females of childbearing potential and sexually active males with partners of reproductive potential: unwilling or unable to use appropriate contraception from screening until at least 30 days after last administration of study treatment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Delcath Systems Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Leslie Callahan, RN

Role: STUDY_DIRECTOR

Delcath Systems

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

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

Tampa, Florida, United States

Site Status

Montefiore Medical Center

New York, New York, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

PHP-HCC-201

Identifier Type: -

Identifier Source: org_study_id