A PHASE 2, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED, INTERNATIONAL, MULTICENTER STUDY OF ORAL TAC 101 AS SECOND LINE TREATMENT IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA WHO RECEIVED SORAFENIB AS FIRST LINE THERAPY

• Conditions: Advanced Hepatocellular carcinoma (HCC); MedDRA version: 9.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectable

• Registration Number: EUCTR2007-007629-32-GB
• Lead Sponsor: Taiho Pharma USA, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03-14
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

Male or female patients who meet all of the following criteria are eligible for enrollment in the
study:
1. Provide written informed consent prior to performance of any study procedures;
2. Is at least 18 years of age;
3. Have a diagnosis of advanced unresectable histologically confirmed HCC (excluding
fibrolamellar carcinoma);
4. Have discontinued from first line treatment with sorafenib monotherapy for any reason
(ie, tumor disease progression, intolerance) at least 14 days prior to planned
randomization but have not received any second line treatment for HCC;
5. Have recovered from any significant sorafenib-related treatment toxicities prior to
randomization (=Grade 1);
6. Have at least 1 target lesion that is viable (has vascularization) and can be accurately
measured according to RECIST;
7. Patients who have received local therapy prior to sorafenib administration (radiation,
surgery, hepatic arterial embolization, chemoembolization, RFA, percutaneous ethanol
injection [PEI] or cryoablation) are eligible. Local therapy must be completed at least
4 weeks prior to the baseline scan;
8. Have ECOG score of 0, 1, or 2;
9. Child-Pugh score <8;
10. Have adequate organ function defined as:
a. Platelet count =50 × 109/L;
b. Hemoglobin =8.0 g/dL;
c. Total bilirubin =3 mg/dL;
d. Alanine transaminase (ALT) and aspartate aminotransferase (AST) =5 × ULN;
e. Serum creatinine =1.5 × ULN;
f. PT-international normalized ratio (INR) =2.3 or PT =6 seconds above control;
g. Total white blood cell (WBC) count =2.0 × 10 E9/L;
11. Is able to take medications orally (eg, no feeding tube); and
12. Women of childbearing potential must have a negative pregnancy test (urine or serum)
prior to randomization within 2 days prior to starting the study drug. Females must agree
to adequate birth control (intrauterine devices excluding those with dispensing hormones,
barrier methods: condom or occlusive cap with spermicidal foam/gel/film/cream/
suppository or true abstinence) if conception is possible during the study. Females must
agree not to become pregnant or intend to become pregnant while taking the study drug
and also for a period of at least 6 months after they have finished taking the study
medication. Males must agree not to impregnate or intend to impregnate their partner
while taking the study drug and for a period of at least 6 months after they have finished
taking the study medication. If their partner is, or could be pregnant, the couple must use
2 barrier methods of contraception in order to prevent transfer of drug related materials to
a fetus in the semen. The use of a condom and an occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/cream/suppository are acceptable double
barrier methods of contraception.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients should be excluded from this study if they do not fulfill the inclusion criteria, or if any of
the following conditions are observed:
1. History of DVT, PE, myocardial infarction (MI), CVA, transitory ischemic attack (TIA),
or any other significant TE during the last 3 years;
2. Have clinically significant symptoms of hepatic encephalopathy or known brain
metastasis;
3. Patients who have had clinically significant acute gastrointestinal bleeding as a result of
portal vein hypertension within 4 weeks prior to randomization are excluded; however,
patients with a history of acute gastrointestinal bleeding that have received appropriate
treatment, ie, ligation of varices, are eligible;
4. Are receiving therapeutic regimens of anticoagulants, with the exception of prophylaxis
care of indwelling venous access devices;
5. Have received a liver transplant;
6. Are taking prohibited medication as described in Section 7.3;
7. Have received a previous systemic therapy (including investigational agents) other than
sorafenib (see Inclusion Criterion 4) for treatment of HCC. Patients participating in
surveys or observational studies are eligible to participate in this study;
8. Have had treatment with any of the following within the specified timeframe prior to
randomization:
a. Any sorafenib within the 14 days prior to randomization;
b. Major surgery within the 4 weeks prior to randomization;
c. Any transfusion, treatment with blood component preparation, received
erythropoietin , albumin preparation, and granulocyte colony-stimulating factor
(G-CSF) within the 2 weeks prior to randomization;
9. Has a serious illness or medical condition(s) including, but not limited to the following:
a. Known gastrointestinal disorder, including malabsorption, chronic nausea, vomiting,
or diarrhea present to the extent that it might interfere with oral intake and absorption
of the study medication;
b. Known human immunodeficiency virus (HIV) or acquired immunodeficiency
syndrome (AIDS)-related illness;
c. Previous or concurrent malignancy except for basal cell carcinoma and/or 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;
d. 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;
e. Has active or uncontrolled clinically serious infection excluding chronic hepatitis;
f. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and in
the judgment of the Investigator would make the patient inappropriate for entry into
this study (eg, active urinary tract infection); or
g. Known allergy or hypersensitivity of TAC-101 and any other components used in the
TAC-101 tablet.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate Overall Survival ;Secondary Objective: To investigate antitumor activity (progression-free survival [PFS] Time to Tumor Progression [TTP])<br>> To assess the adverse event profile and tolerability of TAC 101 as second line treatment;Primary end point(s): The primary efficacy endpoint is Overall Survival. Survival is defined as the time from date of randomization to date of death. In the absence of death confirmation or for patients alive at the time of analysis, survival time will be censored at the date of the last study follow-up.