Back to resultsStudy of TAC-101 as Second Line Treatment in Patients With Advanced Hepatocellular Carcinoma Who Received Sorafenib as First Line Therapy
Primary Purpose
Hepatocellular Carcinoma
Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
TAC-101
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Provide written informed consent prior to performance of any study procedures.
- Is at least 18 years of age.
- Have a diagnosis of advanced unresectable histologically confirmed HCC (excluding fibrolamellar carcinoma).
- 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.
- Have recovered from any significant sorafenib-related treatment toxicities prior to randomization (Grade 1).
- Have at least 1 target lesion that is viable (has vascularization) and can be accurately measured according to RECIST.
- 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.
- Have ECOG score of 0, 1, or 2.
- Child-Pugh score <8.
Have adequate organ function defined as:
- Platelet count great than 50, less than 109/L;
- Hemoglobin 8.0 g/dL;
- Total bilirubin 3 mg/dL;
- Alanine transaminase (ALT) and aspartate aminotransferase (AST) less than or equal to 5 X ULN;
- Serum creatinine 1.5 X ULN;
- PT-international normalized ratio (INR) 2.3 or PT 6 seconds above control
- Total white blood cell (WBC) count 2.0 109/L
- Is able to take medications orally (eg, no feeding tube).
- Women of childbearing potential must have a negative pregnancy test (urine or serum) prior to randomization and within 2 days prior to starting the study drug. Females must agree to adequate non-estrogenic birth control if conception is possible during the study; and males must agree to adequate birth control during the study and up to 6 months after the discontinuation of study medication.
Exclusion Criteria:
- History of DVT, PE, myocardial infarction (MI), CVA, transitory ischemic attack (TIA), or any other significant TE during the last 3 years.
- Have clinically significant symptoms of hepatic encephalopathy or known brain metastasis.
- 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.
- Are receiving therapeutic regimens of anticoagulants, with the exception of prophylaxis care of indwelling venous access devices.
- Have received a liver transplant.
- Are taking prohibited medication.
- 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.
Have had treatment with any of the following within the specified timeframe prior to randomization:
- Any sorafenib within the 14 days prior to randomization.
- Major surgery within the 4 weeks prior to randomization.
- 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.
Has a serious illness or medical condition(s) including, but not limited to the following:
- 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.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
- 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.
- 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.
- Has active or uncontrolled clinically serious infection excluding chronic hepatitis.
- 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).
- Known allergy or hypersensitivity of TAC 101 and any other components used in the TAC 101 tablet.
Sites / Locations
- I.R.C.C.S. San Matteo University Hospital, Golgi
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
TAC-101
Placebo
Arm Description
Participants with advanced hepatocellular carcinoma who had previously received Sorafenib (as first line therapy) were administered a dose of 20 milligram per day (mg/day) of TAC-101 (as second line treatment) oral tablets within 1 hour post morning meals on Days 1 to 14 followed by a recovery period on Days 15 to 21 in 21-day cycle until disease progression or participant met a treatment discontinuation criterion.
Participants with advanced hepatocellular carcinoma who had previously received Sorafenib (as first line therapy) were administered a matching placebo for TAC-101 oral tablets within 1 hour post morning meals on Days 1 to 14 followed by a recovery period from on 15 to 21 in 21-day cycle until disease progression or participant met a treatment discontinuation criterion.
Outcomes
Primary Outcome Measures
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death. Participants who were still alive were censored at the date last known to be alive (last contact date or last follow-up visit).
Secondary Outcome Measures
Radiologic Progression-free Survival (PFS)
PFS was defined as the time from date of randomization to the date of tumor disease progression (ie, radiological only) or death due to any cause. Participants who were alive at the time of analysis and had no signs of tumor progression had their time of PFS censored at the date of the last tumor assessment, unless they received new antitumor therapy.
Time To Progression (TTP)
TTP was defined as time from randomization to the date of tumor progression (radiological only). Participants who were alive with no tumor progression or who died prior to tumor progression had their TTP censored at the date of their last tumor assessment, unless they received new antitumor therapy.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study treatment was considered an AE. A serious AE (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs (both serious/non-serious) that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Change From Baseline in Plasma Levels of the Tumor Marker Alpha-fetoprotein (AFP)
AFP is a tumor marker for hepatocellular carcinoma and elevations in AFP values could precede clinical deterioration and tumor recurrence in participants. Baseline was defined as the last value obtained within 72 hours prior to study treatment administration on Cycle 1 Day 1.
Percent Change From Baseline in Plasma Levels of the Tumor Marker Alpha Fetoprotein-L3 (AFP-L3)
AFP-L3 is a tumor marker for hepatocellular carcinoma and elevations in AFP-L3 values could precede clinical deterioration and tumor recurrence in participants. Baseline was defined as the last value obtained within 72 hours prior to study treatment administration on Cycle 1 Day 1.
Maximum Exposure-response Analysis: Maximum Plasma Concentration (Cmax) of TAC-101
Cmax: maximum plasma concentration; Pharmacokinetic (PK) blood samples were collected at 4 hours (± 1 hour), 8 hours (± 1 hour), and 24 hours (± 1 hour) post-dose on Day 1 of treatment Cycle 1. The 24-hour sample was collected prior to dosing on Day 2.
Overall Exposure-response Analysis: Area Under Curve (AUC0-inf) of TAC-101
AUC(0-inf): Area under the curve from time zero extrapolated to infinity. PK blood samples were collected at 4 hours (± 1 hour), 8 hours (± 1 hour), and 24 hours (± 1 hour) post-dose on Day 1 of treatment Cycle 1. The 24-hour sample was collected prior to dosing on Day 2.
Changes From Baseline in Plasma Insulin-like Growth Factor-2 (IGF-2)
RAR related factors are markers for disease progression in hepatocellular carcinoma participants. In hepatocellular carcinoma participants, IGF-2 is a characteristic biomarkers and its levels are higher in responder cells. The detection of IGF-2 levels showed the efficacy of TAC-101 in IGF-2 influenced malignancy.
Changes From Baseline in Plasma Transforming Growth Factor-beta (TGFβ2)
TGF-β is responsible for tissue regeneration, cell differentiation, embryonic development, and regulation of the immune system. TGF-β2 levels are higher in non-responder cells hence helps in detection of such cells.
Changes From Baseline in Plasma Insulin-like Growth Factor Binding Protein-3 (IGFBP-3)
IGFBP-3 acts as a mediator of antiproliferative signals in hepatocellular carcinoma cells. The inhibition of hepatocellular carcinoma cell proliferation is associated with upregulation of IGFBP-3. Retinoic acid response element (RARE) exists on the promoter region of the IGFBP-3.
Changes From Baseline in Plasma Insulin-like Growth Factor Binding Protein-6 (IGFBP-6)
IGFBP-6 has an IGF-2 binding specificity and inhibits growth of a number of IGF-2-dependent cancers. RARE exists on the promoter region of the IGFBP-6.
Changes From Baseline in Plasma Lactoferrin
RARE exists on the promoter region of the lactoferrin gene.
Changes From Baseline in Plasma Vascular Endothelial Growth Factor-A (VEGF-A)
End of Treatment was defined as "as soon as possible following the last dose of study medication".
Number of Participants With Antitumor Activity After Treatment Discontinuation
Antitumor activity after treatment discontinuation in participant was determined by images, computed tomography (CT), and magnetic resonance imaging (MRI). Tumor imaging was done at Baseline any time within 4 weeks prior to the first dose of study treatment on Cycle 1, Day 1 and every 6 weeks (±1 week) during treatment, regardless of a dose delay. If participant discontinued study treatment for a reason other than disease progression (PD), data collected every 6 weeks until PD and following PD, data collected optionally every 6 weeks until death or up to 1 year after the last participant was randomized.
Relationship Between Tumor Gene Expression of Messenger Ribonucleic Acid (mRNA) Ratio of Co-activators, Co-repressors and Efficacy Parameters
The assessment of correlative factors was to be conducted on tissue removed prior to the study, if available. Tumor tissue assessments included investigation of the relationship between tumor gene mRNA expression of co-activators and co-repressors and efficacy parameters.
Full Information
NCT ID
NCT00687596
First Posted
May 28, 2008
Last Updated
January 3, 2022
Sponsor
Taiho Oncology, Inc.
Collaborators
Quintiles, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00687596
Brief Title
Study of TAC-101 as Second Line Treatment in Patients With Advanced Hepatocellular Carcinoma Who Received Sorafenib as First Line Therapy
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Terminated
Why Stopped
Terminated due to safety concerns
Study Start Date
August 1, 2008 (Actual)
Primary Completion Date
May 10, 2010 (Actual)
Study Completion Date
May 10, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Taiho Oncology, Inc.
Collaborators
Quintiles, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine whether TAC-101 as a second line therapy for participants who received Sorafenib as first line therapy is effective in slowing tumor activity in patients with advanced hepatocellular carcinoma. The study is also looking at the safety of TAC-101 following treatment with Sorafenib.
Detailed Description
Advanced metastatic hepatocellular carcinoma (HCC) is not treatable by surgical approaches or locoregional therapies such as hepatic artery hemoembolization or radiofrequency ablation (RFA) which are effective in controlling localized tumors. Currently marketed systemic chemotherapy agents, with the exception of sorafenib, provide marginal benefit. Despite the demonstrated survival benefit from sorafenib, it is still imperative to improve to the effectiveness of systemic therapy in this patient population. Studies of TAC-101, a synthetic retinoid, indicate that although TAC-101 may not induce tumor regression, it appears to have a stabilizing effect, prolonging survival over what was expected historically. This Phase 2, randomized, double-blind, placebo-controlled international, multicenter study is designed to evaluate the efficacy and safety of TAC 101 as second line treatment in patients with advanced HCC following treatment with sorafenib as first-line therapy. Sorafenib has recently been approved as first line treatment for HCC in the EU and the US and is expected to become the standard of care for the first-line treatment of advanced HCC. Aside from best supportive care, there is no second line therapy available for HCC. It is hypothesized that TAC 101 treatment can extend Overall Survival (OS) after discontinuation of sorafenib.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TAC-101
Arm Type
Experimental
Arm Description
Participants with advanced hepatocellular carcinoma who had previously received Sorafenib (as first line therapy) were administered a dose of 20 milligram per day (mg/day) of TAC-101 (as second line treatment) oral tablets within 1 hour post morning meals on Days 1 to 14 followed by a recovery period on Days 15 to 21 in 21-day cycle until disease progression or participant met a treatment discontinuation criterion.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants with advanced hepatocellular carcinoma who had previously received Sorafenib (as first line therapy) were administered a matching placebo for TAC-101 oral tablets within 1 hour post morning meals on Days 1 to 14 followed by a recovery period from on 15 to 21 in 21-day cycle until disease progression or participant met a treatment discontinuation criterion.
Intervention Type
Drug
Intervention Name(s)
TAC-101
Intervention Description
Participants were randomized to TAC 101 received TAC 101 20 mg (administered as 2 10 mg formulated tablets) PO daily with approximately 240 mL (8 oz) of water under fed conditions (no later than 1 hour after a meal) for 14 days followed by a 7 day recovery period. This cycle was repeated every 21 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants randomized to placebo received 2 placebo tablets (identical in appearance to the TAC 101 tablets) administered PO daily with approximately 240 mL (8 oz) of water under fed conditions (no later than 1 hour after a meal) in a regimen identical to that for TAC 101.
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS was defined as the time from the date of randomization to the date of death. Participants who were still alive were censored at the date last known to be alive (last contact date or last follow-up visit).
Time Frame
From the date of randomization to date of death or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)
Secondary Outcome Measure Information:
Title
Radiologic Progression-free Survival (PFS)
Description
PFS was defined as the time from date of randomization to the date of tumor disease progression (ie, radiological only) or death due to any cause. Participants who were alive at the time of analysis and had no signs of tumor progression had their time of PFS censored at the date of the last tumor assessment, unless they received new antitumor therapy.
Time Frame
From the date of randomization to date of tumor disease progression or death or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)
Title
Time To Progression (TTP)
Description
TTP was defined as time from randomization to the date of tumor progression (radiological only). Participants who were alive with no tumor progression or who died prior to tumor progression had their TTP censored at the date of their last tumor assessment, unless they received new antitumor therapy.
Time Frame
From the date of randomization to date of tumor disease progression or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Description
Any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study treatment was considered an AE. A serious AE (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs (both serious/non-serious) that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Time Frame
From Baseline up to 30 days after the last dose (maximum duration: up to 7.2 months for Placebo and up to 7.9 months for TAC-101)
Title
Change From Baseline in Plasma Levels of the Tumor Marker Alpha-fetoprotein (AFP)
Description
AFP is a tumor marker for hepatocellular carcinoma and elevations in AFP values could precede clinical deterioration and tumor recurrence in participants. Baseline was defined as the last value obtained within 72 hours prior to study treatment administration on Cycle 1 Day 1.
Time Frame
From the date of randomization to date of tumor disease progression or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)
Title
Percent Change From Baseline in Plasma Levels of the Tumor Marker Alpha Fetoprotein-L3 (AFP-L3)
Description
AFP-L3 is a tumor marker for hepatocellular carcinoma and elevations in AFP-L3 values could precede clinical deterioration and tumor recurrence in participants. Baseline was defined as the last value obtained within 72 hours prior to study treatment administration on Cycle 1 Day 1.
Time Frame
From the date of randomization to date of tumor disease progression or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)
Title
Maximum Exposure-response Analysis: Maximum Plasma Concentration (Cmax) of TAC-101
Description
Cmax: maximum plasma concentration; Pharmacokinetic (PK) blood samples were collected at 4 hours (± 1 hour), 8 hours (± 1 hour), and 24 hours (± 1 hour) post-dose on Day 1 of treatment Cycle 1. The 24-hour sample was collected prior to dosing on Day 2.
Time Frame
Cycle 1-day 1: 4, 8, and 24 hours after the first dose of study drug
Title
Overall Exposure-response Analysis: Area Under Curve (AUC0-inf) of TAC-101
Description
AUC(0-inf): Area under the curve from time zero extrapolated to infinity. PK blood samples were collected at 4 hours (± 1 hour), 8 hours (± 1 hour), and 24 hours (± 1 hour) post-dose on Day 1 of treatment Cycle 1. The 24-hour sample was collected prior to dosing on Day 2.
Time Frame
Cycle 1-day 1: 4, 8, and 24 hours after the first dose of study drug
Title
Changes From Baseline in Plasma Insulin-like Growth Factor-2 (IGF-2)
Description
RAR related factors are markers for disease progression in hepatocellular carcinoma participants. In hepatocellular carcinoma participants, IGF-2 is a characteristic biomarkers and its levels are higher in responder cells. The detection of IGF-2 levels showed the efficacy of TAC-101 in IGF-2 influenced malignancy.
Time Frame
From Baseline up to end of study treatment or up to tumor disease progression or up to death or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)
Title
Changes From Baseline in Plasma Transforming Growth Factor-beta (TGFβ2)
Description
TGF-β is responsible for tissue regeneration, cell differentiation, embryonic development, and regulation of the immune system. TGF-β2 levels are higher in non-responder cells hence helps in detection of such cells.
Time Frame
From Baseline up to end of study treatment or up to tumor disease progression or up to death or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)
Title
Changes From Baseline in Plasma Insulin-like Growth Factor Binding Protein-3 (IGFBP-3)
Description
IGFBP-3 acts as a mediator of antiproliferative signals in hepatocellular carcinoma cells. The inhibition of hepatocellular carcinoma cell proliferation is associated with upregulation of IGFBP-3. Retinoic acid response element (RARE) exists on the promoter region of the IGFBP-3.
Time Frame
From Baseline up to end of study treatment or up to tumor disease progression or up to death or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)
Title
Changes From Baseline in Plasma Insulin-like Growth Factor Binding Protein-6 (IGFBP-6)
Description
IGFBP-6 has an IGF-2 binding specificity and inhibits growth of a number of IGF-2-dependent cancers. RARE exists on the promoter region of the IGFBP-6.
Time Frame
From Baseline up to end of study treatment or up to tumor disease progression or up to death or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)
Title
Changes From Baseline in Plasma Lactoferrin
Description
RARE exists on the promoter region of the lactoferrin gene.
Time Frame
From Baseline up to end of study treatment or up to tumor disease progression or up to death or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)
Title
Changes From Baseline in Plasma Vascular Endothelial Growth Factor-A (VEGF-A)
Description
End of Treatment was defined as "as soon as possible following the last dose of study medication".
Time Frame
From Baseline up to end of study treatment or up to tumor disease progression or up to death or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)
Title
Number of Participants With Antitumor Activity After Treatment Discontinuation
Description
Antitumor activity after treatment discontinuation in participant was determined by images, computed tomography (CT), and magnetic resonance imaging (MRI). Tumor imaging was done at Baseline any time within 4 weeks prior to the first dose of study treatment on Cycle 1, Day 1 and every 6 weeks (±1 week) during treatment, regardless of a dose delay. If participant discontinued study treatment for a reason other than disease progression (PD), data collected every 6 weeks until PD and following PD, data collected optionally every 6 weeks until death or up to 1 year after the last participant was randomized.
Time Frame
From the date of treatment discontinuation to date of tumor disease progression or death or up to 1 year post last participant was randomized, whichever was earlier (maximum duration: up to 21.3 months)
Title
Relationship Between Tumor Gene Expression of Messenger Ribonucleic Acid (mRNA) Ratio of Co-activators, Co-repressors and Efficacy Parameters
Description
The assessment of correlative factors was to be conducted on tissue removed prior to the study, if available. Tumor tissue assessments included investigation of the relationship between tumor gene mRNA expression of co-activators and co-repressors and efficacy parameters.
Time Frame
At Baseline (prior to treatment after consenting informed consent form [ICF]) up to last dose of study treatment, assessed every 6 weeks (maximum duration: up to 21.3 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provide written informed consent prior to performance of any study procedures.
Is at least 18 years of age.
Have a diagnosis of advanced unresectable histologically confirmed HCC (excluding fibrolamellar carcinoma).
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.
Have recovered from any significant sorafenib-related treatment toxicities prior to randomization (Grade 1).
Have at least 1 target lesion that is viable (has vascularization) and can be accurately measured according to RECIST.
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.
Have ECOG score of 0, 1, or 2.
Child-Pugh score <8.
Have adequate organ function defined as:
Platelet count great than 50, less than 109/L;
Hemoglobin 8.0 g/dL;
Total bilirubin 3 mg/dL;
Alanine transaminase (ALT) and aspartate aminotransferase (AST) less than or equal to 5 X ULN;
Serum creatinine 1.5 X ULN;
PT-international normalized ratio (INR) 2.3 or PT 6 seconds above control
Total white blood cell (WBC) count 2.0 109/L
Is able to take medications orally (eg, no feeding tube).
Women of childbearing potential must have a negative pregnancy test (urine or serum) prior to randomization and within 2 days prior to starting the study drug. Females must agree to adequate non-estrogenic birth control if conception is possible during the study; and males must agree to adequate birth control during the study and up to 6 months after the discontinuation of study medication.
Exclusion Criteria:
History of DVT, PE, myocardial infarction (MI), CVA, transitory ischemic attack (TIA), or any other significant TE during the last 3 years.
Have clinically significant symptoms of hepatic encephalopathy or known brain metastasis.
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.
Are receiving therapeutic regimens of anticoagulants, with the exception of prophylaxis care of indwelling venous access devices.
Have received a liver transplant.
Are taking prohibited medication.
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.
Have had treatment with any of the following within the specified timeframe prior to randomization:
Any sorafenib within the 14 days prior to randomization.
Major surgery within the 4 weeks prior to randomization.
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.
Has a serious illness or medical condition(s) including, but not limited to the following:
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.
Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
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.
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.
Has active or uncontrolled clinically serious infection excluding chronic hepatitis.
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).
Known allergy or hypersensitivity of TAC 101 and any other components used in the TAC 101 tablet.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Taiho Central
Organizational Affiliation
Taiho Oncology, Inc. USA
Official's Role
Study Director
Facility Information:
Facility Name
I.R.C.C.S. San Matteo University Hospital, Golgi
City
Pavia
ZIP/Postal Code
27100
Country
Italy
12. IPD Sharing Statement
Learn more about this trial
Study of TAC-101 as Second Line Treatment in Patients With Advanced Hepatocellular Carcinoma Who Received Sorafenib as First Line Therapy
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