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Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of TAC-101 in Combination With Transcatheter Arterial Chemoembolization (TACE) Versus TACE Alone in Asian Patients With Advanced Hepatocellular Carcinoma


Phase 2
18 Years
N/A
Not Enrolling
Both
Advanced Hepatocellular Carcinoma

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Trial Information

Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of TAC-101 in Combination With Transcatheter Arterial Chemoembolization (TACE) Versus TACE Alone in Asian Patients With Advanced Hepatocellular Carcinoma


Transcatheter arterial chemoembolization (TACE) is a commonly performed procedure in the
treatment of unresectable liver tumors for selected patients. TACE is a major palliative
treatment for these patients. Most patients will have intrahepatic recurrence of their
tumors following TACE. In this study, which will be conducted in Asian countries excluding
Japan, TAC-101 will be administered as maintenance therapy after TACE compared with placebo
therapy after TACE to patients with advanced HCC who are being scheduled for TACE and who
either have not had any previous TACE procedures or who received their most recent TACE at
least 120 days before signing the Informed Consent Form (ICF) and the TACE procedure
resulted in complete necrosis, to determine if TAC-101 will enhance the benefits of TACE.


Inclusion Criteria:



- A patient must meet all of the following inclusion criteria to be eligible for
enrollment in this study and before undergoing the first TACE procedure of this
study:

1. Has an HCC diagnosis by histology (can not have a mixed tumor type such as HCC
and cholangiocarcinoma) OR by the following non-invasive criteria observed
either within 14 days prior to first TACE or in the past.

- One imaging technique (CT scan or magnetic resonance imaging [MRI] both
with unenhanced plus hepatic arterial phase and portal venous phases)
showing characteristic features in a focal lesion > 20 mm with arterial
vascularization, or

- Two dynamic imaging techniques (CT scan, MRI with unenhanced plus hepatic
arterial phase and portal venous phases) showing characteristic features
coincidentally in a focal lesion 10-20 mm with arterial vascularization.

2. Is TACE naïve or has received the most recent TACE procedure, which showed
complete necrosis after treatment, at least 120 days before signing ICF.

3. Eligible to receive TACE and being scheduled to receive TACE.

4. Is ≥ 18 years of age.

5. Is not amenable to treatment with curative surgery, transplant, or percutaneous
ablation, including RFA, percutaneous ethanol injection therapy (PEIT) and
percutaneous microwave coagulation therapy (PMCT).

6. Have at least 1 measurable lesion that is ≥10 mm in size. Measurable lesions
must be confirmed nodular type (not including only infiltration type) which
demonstrated substantial hypervascularity by CT scan or MRI both with unenhanced
plus hepatic arterial phase and portal venous phases. All measurable lesions
must be targeted by the first TACE in this study

- If there are ≥ 4 intrahepatic lesions, at least 1 must be ≥10 mm and all
lesions must be <100 mm.

- If there are < 4 intrahepatic lesions, at least one must be ≥ 30 mm and all
lesions must be <100 mm.

- No vascular invasion in main trunk and first order branch of portal vein or
other large vessels (hepatic vein or inferior vena cava).

- No extrahepatic tumor spread

7. Absence of extrahepatic abdominal tumors must be confirmed.

8. Has adequate organ function as defined by the following criteria:

- White blood cell (WBC) count > 3,000/mm3

- Platelet count > 60,000/mm3

- Hemoglobin > 8.0 grams (g)/deciliter (dL)

- Aspartate transaminase (AST) < 5 x ULN

- Alanine transaminase (ALT) < 5 x ULN

- Total bilirubin < 2.0 mg/dL

- Albumin > 2.8 g/dL

- Serum creatinine < 1.5 mg/dL

- International normalized ratio (INR) ≤ 2.0

- Triglyceride ≤ 2.5 x ULN.

9. Has a Child-Pugh classification of ≤ 8.

10. Has a Cancer of the Liver Italian Program (CLIP)68 score of 0, 1, 2 or 3.

11. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

12. Is willing and able to comply with schedule visits, treatment plans, laboratory
tests, and other study procedures.

13. Provides written informed consent prior to the implementation of any study
assessment or procedures.

Exclusion Criteria:

- Patients will be excluded from participation in the study if any of the following
conditions are observed before undergoing the first TACE procedure:

1. Has only infiltration type of HCC.

2. Has extrahepatic metastasis of HCC including regional lymph node metastases.

3. Has had systemic chemotherapy (eg, sorafenib, doxorubicin), immunotherapy, or
biologic therapy or radiotherapy for HCC, or treatment with TAC-101.

4. Received treatment with any of the following within the specified time frame:

- Any major surgical procedure within 28 days prior to signing the ICF

- Any red blood cell or thrombocyte transfusion, treatment with blood
component preparation, albumin preparation, Granulocyte-Colony Stimulating
Factor (G-CSF), or erythropoietin within 14 days prior to signing the ICF

- Any intra-arterial chemotherapy (transcatheter injection) using lipiodol
for HCC performed within 119 days prior to signing ICF.

- Any local therapy such as alcohol injection, radiofrequency/ultrasound
ablation, intraarterial chemotherapy (transcatheter arterial injection) for
HCC performed within 28 days prior to signing the ICF

- Any investigational agent within 28 days prior to signing the ICF

5. Has ascites, pleural effusions or pericardial fluid refractory to diuretic
therapy.

6. Has clinical symptoms of hepatic encephalopathy.

7. Has active or uncontrolled clinically serious infection excluding chronic
hepatitis.

8. Has a history of gastrointestinal (GI) bleeding in last 3 months.

9. Has previous or concurrent malignancy except for in situ carcinoma of the
cervix, or other solid tumor treated curatively and without evidence of
recurrence for at least 3 years prior to the study.

10. Has uncontrolled metabolic disorders or other nonmalignant organ or systemic
diseases or secondary effects of cancer that induce a high medical risk and/or
make assessment of survival uncertain.

11. Has any history during the last 3 years of deep vein thrombosis (DVT), pulmonary
embolism (PE), myocardial infarction (MI), cerebrovascular accident (CVA),
transient ischemic attack (TIA), unstable angina pectoris, or any other
significant thromboembolic event (TE).

12. Has ejection fraction (EF) by echocardiogram (ECHO) or multi-gate acquisition
(MUGA) that is outside of the normal range according to the site's institutional
standard.

13. Has GI disease resulting in an inability to take oral medication.

14. Has had a liver transplant.

15. Has known allergy or hypersensitivity to TAC-101, doxorubicin, epirubicin, other
anthracyclines, anthracenediones or any of the components used in the study drug
formulations.

16. Has known hypersensitivity to iodinated contrast medium.

17. Is receiving therapeutic regimens of anticoagulants. However, use of low dose
anticoagulants for prophylactic care of indwelling venous access device and use
of low dose aspirin for prophylaxis are permitted.

18. Is taking medication known or suspected to predispose patient to an increased
risk of VTE (eg, oral contraceptives, hormone replacement therapy, megestrol
acetate).

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

radiologically proven progression-free survival (PFS)

Outcome Time Frame:

Tumor Imaging assessments will be conducted at screening/baseline within 14 days prior to first TACE; every 8 weeks during treatment within 14 days prior to first TACE and every 8 weeks during follow-up period within 14 days prior to first TACE.

Safety Issue:

No

Principal Investigator

Fabio Benedetti, MD

Investigator Role:

Study Director

Investigator Affiliation:

Taiho Pharma USA, Inc.

Authority:

United States: Food and Drug Administration

Study ID:

TAC101-204

NCT ID:

NCT00756782

Start Date:

October 2008

Completion Date:

December 2008

Related Keywords:

  • Advanced Hepatocellular Carcinoma
  • hepatocellular carcinoma
  • Carcinoma
  • Carcinoma, Hepatocellular

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