Clinical trial NCT02007954: Doxorubicin-eluting LC Bead M1 for Patients With Hepatocellular Carcinoma
Official title: Doxorubicin-eluting LC Bead M1 for Patients With Hepatocellular Carcinoma (DEBDOX)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: HCC
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2013-12-11
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: INCLUSION CRITERIA:

1. The patient has preserved liver function (Child-Pugh A-B class) without significant liver decompensation.
2. The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at study entry.
3. The patient is age 18 years or older.
4. The patient has a life expectancy of \> 12 weeks.
5. 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).
6. 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.
7. 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).
8. The patient has adequate renal function, as defined by the following criteria:

   * Serum creatinine \</= 2.0 x the institutional ULN
9. The patient has a baseline international normalized ratio (INR) \< 1.5.
10. The patient, if a woman of childbearing potential, has a negative pregnancy test.
11. The patient is able to give written informed consent.
12. The patient is willing and able to comply with study procedures, scheduled visits, and treatment plans.
13. Patients with early stage HCC may be included in the protocol to receive DEBDOX-M1 prior to resection

EXCLUSION CRITERIA:

1. 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).
2. The patient is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, targeted therapy, or an investigational agent.
3. The patient has extrahepatic, metastatic, symptomatic HCC. Enlarged reactive lymph nodes, or indeterminate lesions, such as lung nodules are acceptable.
4. The patient's tumor has replaced \>70% of the liver volume.
5. The patient has clinically significant ascites. Trace ascites on imaging is acceptable.
6. Marco-shunting noted on the hepatic angiogram.
7. The patient has untreatable bleeding diathesis.
8. The patient has complete main portal vein thrombosis with reversal of flow.
9. The patient has a left ventricle ejection fraction of less than 45%.
10. The patient has evidence of clinically significant peripheral vascular disease.
11. 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)
    * Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment \[NCI-CTCAE Grade 3\] or asymptomatic sustained ventricular tachycardia)
    * Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements
12. There is evidence of substance abuse or medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of study results.
13. The patient is pregnant or breast-feeding.
14. The patient is allergic to contrast media that cannot be readily prevented with premedication or managed.
15. The patient has extra-hepatic, metastatic, and symptomatic HCC.

Primary outcomes:
measure: Success of DEBDOX-M1 Procedure as a Measure of Feasibility
timeFrame: 6 months
measure: Collection of Adverse Events Related to Study Device as a Measure of Safety
timeFrame: 1 month
Secondary outcomes:
measure: Efficacy - Tumor Response by EASL
timeFrame: 1 month
measure: Efficacy - Tumor Response by qEASL
timeFrame: 1 month
measure: Efficacy - Tumor Response by mRECIST
timeFrame: 1 month
measure: Efficacy - Number of Patients Downstaged or Bridged to Surgical Interventions
timeFrame: 6 months
measure: AFP Tumor Marker Pre- and Post-treatment
timeFrame: 1 month
Other outcomes:
measure: Exploratory Endpoint - Pharmacokinetic (PK) Profile of Doxorubicin and Doxorubicinol Post DEBDOX-M1 TACE
timeFrame: 24 hours
measure: Exploratory Endpoint - Total Drug Exposure Over Time (AUC) of Doxorubicin and Doxorubicinol Post TACE
timeFrame: 24 hours
measure: Exploratory Endpoint - Tmax of Doxorubicin and Doxorubicinol Post DEBDOX-M1 TACE
timeFrame: 24 hours
Locations:
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Jeff Geschwind, MD
role: PRINCIPAL_INVESTIGATOR
References: