Advanced Hepatocellular CarcinomaPhase 2NCT00756782
A Study of TAC-101 in Combination With TACE Versus TACE Alone in Asian Patients With Advanced Hepatocellular Carcinoma
A Phase 2 study testing TAC-101 in people with Advanced Hepatocellular Carcinoma, run by Taiho Oncology, Inc..
Trial summary
The purpose of this study is to evaluate the efficacy and safety of TAC-101 after Transcatheter Arterial Chemoembolization (TACE) in patients with advanced, unresectable hepatocellular carcinoma (HCC) who are being scheduled for TACE. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Hepatocellular Carcinoma
- What is being tested?
- TAC-101
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Oct 2008to Dec 2008
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -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:
- 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.
- Is TACE naïve or has received the most recent TACE procedure, which showed complete necrosis after treatment, at least 120 days before signing ICF.
- Eligible to receive TACE and being scheduled to receive TACE.
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- Is ≥ 18 years of age.
- 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).
- 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
- Absence of extrahepatic abdominal tumors must be confirmed.
- 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.
- Has a Child-Pugh classification of ≤ 8.
- Has a Cancer of the Liver Italian Program (CLIP)68 score of 0, 1, 2 or 3.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Is willing and able to comply with schedule visits, treatment plans, laboratory tests, and other study procedures.
- Provides written informed consent prior to the implementation of any study assessment or procedures.
Who cannot join
- Patients will be excluded from participation in the study if any of the following conditions are observed before undergoing the first TACE procedure:
- Has only infiltration type of HCC.
- Has extrahepatic metastasis of HCC including regional lymph node metastases.
- Has had systemic chemotherapy (eg, sorafenib, doxorubicin), immunotherapy, or biologic therapy or radiotherapy for HCC, or treatment with TAC-101.
- Received treatment with any of the following within the specified time frame:
- Any major surgical procedure within 28 days prior to signing the ICF
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- 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
- Has ascites, pleural effusions or pericardial fluid refractory to diuretic therapy.
- Has clinical symptoms of hepatic encephalopathy.
- Has active or uncontrolled clinically serious infection excluding chronic hepatitis.
- Has a history of gastrointestinal (GI) bleeding in last 3 months.
- 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.
- 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.
- 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).
- 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.
- Has GI disease resulting in an inability to take oral medication.
- Has had a liver transplant.
- Has known allergy or hypersensitivity to TAC-101, doxorubicin, epirubicin, other anthracyclines, anthracenediones or any of the components used in the study drug formulations.
- Has known hypersensitivity to iodinated contrast medium.
- 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.
- Is taking medication known or suspected to predispose patient to an increased risk of VTE (eg, oral contraceptives, hormone replacement therapy, megestrol acetate).
About this study
Official title: 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
The purpose of this study is to evaluate the efficacy and safety of TAC-101 after Transcatheter Arterial Chemoembolization (TACE) in patients with advanced, unresectable hepatocellular carcinoma (HCC) who are being scheduled for TACE.
Read the detailed description
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.
- Conditions
- Advanced Hepatocellular Carcinoma
- Being tested
- TAC-101, Placebo
- Keywords
- hepatocellular carcinoma
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAC-101Drug
Patients will receive TAC-101 20 mg (2 x 10-mg formulated tablets) administered orally every day with approximately 8 oz. water within 1 hour following a morning meal for 14 days followed by a 7-day recovery period, repeated every 21 days.
PlaceboDrug
Patients will receive placebo (two matching tablets) at same frequency and duration of active treatment
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Patients will receive TAC-101 20 mg (2 x 10-mg formulated tablets) administered orally every day with approximately 8 oz. water within 1 hour following a morning meal for 14 days followed by a 7-day recovery period, repeated every 21 days Receives: Drug: TAC-101 |
| B | Placebo comparator | Patients will receive placebo (two matching tablets) at same frequency and duration of active treatment Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
radiologically proven progression-free survival (PFS)
Measured: 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.
Secondary outcomes (9)
Overall survival (OS)
Measured: Survival status obtained every 8 weeks during imaging follow-up period, from first TACE, patients contacted every 12 weeks until death or for at least 3 yrs after randomization of the last patient.
Time to appearance of remote new lesions (TTNLr)
Measured: 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.
Objective tumor response rate (ORR) according to RECIST criteria (CR + PR)
Measured: 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.
Effects on the plasma levels of alpha-fetoprotein (AFP and AFP-L3)
Measured: Blood samples for AFP and AFP-L3assessment obtained at Screening/ Baseline; every 8 weeks after first TACE during the treatment period; at the end of the treatment period; and every 8 weeks (± 2 weeks) from first TACE during imaging f/up period.
Number of post-randomization TACE procedures
Measured: The number of post-randomization TACE procedures per patient in the double-blind treatment period patient will be counted every 8 weeks during treatment from first TACE.
The adverse event (AE) profile and tolerability of TAC-101 therapy with TACE versus placebo therapy with TACE
Measured: AEs will be reported from the time a patient signs ICF through the period of patient follow-up (30 days after the last dose of study medication).
The relationship between the PK of TAC-101 and its metabolites and safety and efficacy parameters, including hepatic function
Measured: Pharmacokinetic blood samples will be collected (optional) 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 must be collected prior to dosing on Day 2.
The biological effects of TAC-101 on selected RAR-related factors and growth factor VEGF-A
Measured: Blood samples collected at Screening/Baseline; every 8 weeks (± 2 weeks) after first TACE during the treatment period; at the end of the treatment period; at the Safety Follow-up visit (30 days after the end of study treatment).
The relationship between tumor gene expression (mRNA expression) of co-activators and co-repressors and efficacy parameters
Measured: Tissue samples collected at Screening/Baseline.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2008 (estimated)
- Study startOct 2008
- Primary completionDec 2008
- Study completionDec 2008
Why it stopped: Terminated due to safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Taiho Oncology, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taiho Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Fabio Benedetti, MD, Study director, Taiho Oncology, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00756782
- Sponsor's protocol ID
- TAC101-204
- Status last verified
- Aug 2024
- First submitted
- 19 Sep 2008
- Last updated
- 4 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00756782
- Acronym / sponsor ID
- TAC101-204
- Conditions
- Advanced Hepatocellular Carcinoma
- Keywords
- hepatocellular carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Terminated due to safety concerns.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Taiho Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2008
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 22 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of TAC-101 after Transcatheter Arterial Chemoembolization (TACE) in patients with advanced, unresectable hepatocellular carcinoma (HCC) who are being scheduled for TACE.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: TAC-101Patients will receive TAC-101 20 mg (2 x 10-mg formulated tablets) administered orally every day with approximately 8 oz. water within 1 hour following a morning meal for 14 days followed by a 7-day recovery period, repeated every 21 days |
| B | Placebo comparator | Drug: PlaceboPatients will receive placebo (two matching tablets) at same frequency and duration of active treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- -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:
- 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.
- Is TACE naïve or has received the most recent TACE procedure, which showed complete necrosis after treatment, at least 120 days before signing ICF.
- Eligible to receive TACE and being scheduled to receive TACE.
- Is ≥ 18 years of age.
Key exclusion criteria (24 listed)
- Patients will be excluded from participation in the study if any of the following conditions are observed before undergoing the first TACE procedure:
- Has only infiltration type of HCC.
- Has extrahepatic metastasis of HCC including regional lymph node metastases.
- Has had systemic chemotherapy (eg, sorafenib, doxorubicin), immunotherapy, or biologic therapy or radiotherapy for HCC, or treatment with TAC-101.
- Received treatment with any of the following within the specified time frame:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAC-101Patients will receive TAC-101 20 mg (2 x 10-mg formulated tablets) administered orally every day with approximately 8 oz. water within 1 hour following a morning meal for 14 days followed by a 7-day recovery period, repeated every 21 days. | Drug | A |
| PlaceboPatients will receive placebo (two matching tablets) at same frequency and duration of active treatment | Drug | B |
Primary outcome
radiologically proven progression-free survival (PFS)
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.
9 secondary outcomes
Overall survival (OS)
Time frame: Survival status obtained every 8 weeks during imaging follow-up period, from first TACE, patients contacted every 12 weeks until death or for at least 3 yrs after randomization of the last patient.
Time to appearance of remote new lesions (TTNLr)
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.
Objective tumor response rate (ORR) according to RECIST criteria (CR + PR)
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.
Effects on the plasma levels of alpha-fetoprotein (AFP and AFP-L3)
Time frame: Blood samples for AFP and AFP-L3assessment obtained at Screening/ Baseline; every 8 weeks after first TACE during the treatment period; at the end of the treatment period; and every 8 weeks (± 2 weeks) from first TACE during imaging f/up period.
Number of post-randomization TACE procedures
Time frame: The number of post-randomization TACE procedures per patient in the double-blind treatment period patient will be counted every 8 weeks during treatment from first TACE.
The adverse event (AE) profile and tolerability of TAC-101 therapy with TACE versus placebo therapy with TACE
Time frame: AEs will be reported from the time a patient signs ICF through the period of patient follow-up (30 days after the last dose of study medication).
The relationship between the PK of TAC-101 and its metabolites and safety and efficacy parameters, including hepatic function
Time frame: Pharmacokinetic blood samples will be collected (optional) 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 must be collected prior to dosing on Day 2.
The biological effects of TAC-101 on selected RAR-related factors and growth factor VEGF-A
Time frame: Blood samples collected at Screening/Baseline; every 8 weeks (± 2 weeks) after first TACE during the treatment period; at the end of the treatment period; at the Safety Follow-up visit (30 days after the end of study treatment).
The relationship between tumor gene expression (mRNA expression) of co-activators and co-repressors and efficacy parameters
Time frame: Tissue samples collected at Screening/Baseline.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fabio Benedetti, MD study director
Taiho Oncology, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TAC-101 in people with Advanced Hepatocellular Carcinoma, run by Taiho Oncology, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 4 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
radiologically proven progression-free survival (PFS) (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2024.