Doxorubicin-eluting LC Bead M1 for Patients With Hepatocellular Carcinoma

NCT02007954 | Completed Phase 2 Results DMC

• 2 other identifiers: J1306NA_00077927
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the feasibility and safety of using small beads (70-150 micron in place of 100-300 micron) to deliver chemotherapy into the liver to treat patients with hepatocellular carcinoma (HCC). The beads (LC-Bead M1) will be loaded with doxorubicin (DEBDOX-M1), and used to administer transarterial chemoembolization (TACE) DEBDOX, loaded with doxorubicin, is a device that utilizes tiny beads (70-150 microns) to deliver chemotherapy agents into liver tumor(s) via the hepatic artery. This device allows for continuous release of doxorubicin into the liver tumor tissue(s) causing necrosis of the targeted tumor(s). The potential advantages of the smaller beads are deeper penetration into the tumor bed, while avoiding premature proximal occlusion of vessels feeding the tumor, and more consistent dosing. Response to therapy will be evaluated monthly by clinic visits and blood tests (to include assessment of liver function and tumor markers) and by imaging (usually MRIs) every 1-2 months. Patients will be on study for 6 months after which they will be exited from the study and followed for survival. Once exited from the study they will continue to be eligible to receive the smaller beads (DEBDOX), should it be recommended.

Conditions

Hepatocellular Carcinoma

Keywords

HCC

Outcome Measures

Primary Outcomes (2)

• Success of DEBDOX-M1 Procedure as a Measure of Feasibility

  Feasibility is defined as achieving an acceptable level of technical success in the use of DEBDOX-M1 beads treating hepatic lesions in patients with hepatocellular carcinoma.

  6 months

• Collection of Adverse Events Related to Study Device as a Measure of Safety

  For safety, all toxicities assessed as being at least possibly related will be analyzed by descriptive statistics to show type, grade (NCI Common Toxicity Criteria v.4 toxicity criteria), frequency and time from DEBDOX-M1TACE.

  1 month

Secondary Outcomes (5)

• Efficacy - Tumor Response by EASL

  1 month

• Efficacy - Tumor Response by qEASL

  1 month

• Efficacy - Tumor Response by mRECIST

  1 month

• Efficacy - Number of Patients Downstaged or Bridged to Surgical Interventions

  6 months

• AFP Tumor Marker Pre- and Post-treatment

  1 month

Other Outcomes (3)

• Exploratory Endpoint - Pharmacokinetic (PK) Profile of Doxorubicin and Doxorubicinol Post DEBDOX-M1 TACE

  24 hours

• Exploratory Endpoint - Total Drug Exposure Over Time (AUC) of Doxorubicin and Doxorubicinol Post TACE

  24 hours

• Exploratory Endpoint - Tmax of Doxorubicin and Doxorubicinol Post DEBDOX-M1 TACE

  24 hours

Study Arms (1)

DEBDOX

EXPERIMENTAL

Device: DEBDOX

Interventions

DEBDOX DEVICE

DEBDOX, loaded with doxorubicin, is a device that utilizes beads in place of lipiodol to deliver the chemotherapy into the liver tumor. The device allows for continuous elution of doxorubicin into the liver tumor tissue. The advantages of this method of delivery in comparison to conventional TACE are that the beads are able to deliver a greater volume and concentration of the drugs to the tumor because of their unique ability to elute the drug over a period of several days. As a result of this unique delivery, systemic toxicity is significantly reduced. The potential advantages of the smaller beads are deeper penetration into the tumor bed, while avoiding premature proximal occlusion of vessels feeding the tumor, and more consistent dosing. These properties translate into greater potency of therapy and potentially improved patient survival.

DEBDOX

Eligibility Criteria

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

You may qualify if:

• The patient has preserved liver function (Child-Pugh A-B class) without significant liver decompensation.
• The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at study entry.
• The patient is age 18 years or older.
• The patient has a life expectancy of \> 12 weeks.
• The patient has measurable or evaluable disease that will be directly treated with intrahepatic therapy (as defined by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1).
• The patient has adequate hematologic function as defined by the following criteria:
• An absolute neutrophil count (ANC) ≥ 1500/micro L,
• Hemoglobin ≥ 9.5 g/dL, and a
• Platelet count ≥ 50,000/micro L.
• The patient has adequate hepatic function, as defined by the following criteria:
• Total bilirubin \</= 3.0 mg/dL
• Aspartate transaminase (AST) and alanine transaminase (ALT) \</= 8 x the upper limit of normal (ULN).
• The patient has adequate renal function, as defined by the following criteria:
• Serum creatinine \</= 2.0 x the institutional ULN
• The patient has a baseline international normalized ratio (INR) \< 1.5.

You may not qualify if:

• The patient has a history of another primary cancer (ie, a primary cancer not associated with the patient's current liver tumor), with the exception of (a) curatively resected nonmelanomatous skin cancer; (b) curatively treated cervical carcinoma in situ; or (c) other primary solid tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years prior to enrollment (date of informed consent).
• The patient is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, targeted therapy, or an investigational agent.
• The patient has extrahepatic, metastatic, symptomatic HCC. Enlarged reactive lymph nodes, or indeterminate lesions, such as lung nodules are acceptable.
• The patient's tumor has replaced \>70% of the liver volume.
• The patient has clinically significant ascites. Trace ascites on imaging is acceptable.
• Marco-shunting noted on the hepatic angiogram.
• The patient has untreatable bleeding diathesis.
• The patient has complete main portal vein thrombosis with reversal of flow.
• The patient has a left ventricle ejection fraction of less than 45%.
• The patient has evidence of clinically significant peripheral vascular disease.
• The patient has clinically significant or symptomatic extrahepatic disease, for example, an uncontrolled inter-current illness including, but not limited to:
• Ongoing or active infection requiring parenteral antibiotics
• Symptomatic congestive heart failure (class II to IV of the New York Heart Association classification for heart disease)
• Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
• Uncontrolled hypertension (systolic blood pressure \> 150 mmHg, diastolic blood pressure \> 90 mmHg, found on 2 consecutive measurements separated by a 1-week period despite adequate medical support)

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

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

Results Point of Contact

• Title: Jean-Francois Geschwind, MD
• Organization: Yale University

jeff.geschwind@yale.edu

203-785-5865

Study Officials

• Jeff Geschwind, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: November 21, 2013
• First Posted: December 11, 2013
• Study Start: February 1, 2014
• Primary Completion: August 11, 2015
• Study Completion: November 18, 2016
• Last Updated: August 11, 2017
• Results First Posted: August 11, 2017

Record last verified: 2014-07

Locations

US (1)