Doxorubicin-eluting LC Bead M1 for Patients With Hepatocellular Carcinoma
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: DEBDOX
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HCC

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.