Hepatocellular CarcinomaPhase 2/3NCT02240771
Transarterial Chemotherapy Compared With Oral Chemotherapy in the Treatment of Advanced Hepatocellular Carcinoma
A Phase 2/3 study testing Transarterial chemotherapy and Oral chemotherapy in people with Hepatocellular Carcinoma, run by All India Institute of Medical Sciences at 1 site in India.
Trial summary
In India, majority of our patients have advanced hepatocellular carcinoma (HCC) at presentation and hence are unsuitable for the available curative treatment options. In such patients the treatment options are mainly palliative. Read more about this study
- Who is it for?
- Ages 12 to 80 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Transarterial chemotherapy and Oral chemotherapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 124 participants
- Where
- 1 siteIndia
- Study dates
- Jan 2006to Mar 2015
- Phase
- Phase 2/3
- 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 12 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients above 12 years of age with performance status (PST) score of 0-2
- Unresectable HCC with underlying Child's A/B cirrhosis
- Blocked Main portal vein
- No history of drug allergy
- Informed written consent of patient.
Who cannot join
- Child's C cirrhosis
- Performance status 3-5
- Extra hepatic disease
- Co-morbid illness like coronary artery disease, congestive heart failure, chronic renal failure etc
- Previous history of encephalopathy/ upper gastrointestinal bleed in the last six months
- Pregnancy
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
AII India Institute of Medical Sciences
New Delhi, National Capital Territory of Delhi, 110029
Subrat K Acharya, DM, +91-11-26594934, subratacharya2004@yahoo.com
Shalimar . ., DM, +91-9968405815, drshalimar@yahoo.com
About this study
Official title: Randomized Control Trial of Transarterial Chemotherapy (TAC) Versus Oral Thalidomide and Capecitabine in the Treatment of Unresectable Hepatocellular Carcinoma
In India, majority of our patients have advanced hepatocellular carcinoma (HCC) at presentation and hence are unsuitable for the available curative treatment options. In such patients the treatment options are mainly palliative. Transarterial chemoembolization (TACE), transarterial chemotherapy (TAC) and various forms of oral chemotherapy are the only available options currently. Many patients have more advanced disease with the involvement of branches of portal vein. This further limits the therapeutic options. According to Barcelona Clinic Liver Cancer (BCLC) staging, involvement of portal vein precludes any standard form of therapy. TAC and oral chemotherapy has been tried in this group of patients by few researchers. Which treatment (TAC or oral chemotherapy) would be better suitable for advanced stage (BCLC C) needs to be explored. However, there are no randomized controlled trials (RCT's) available.
TAC is the procedure for treating patients of HCC with portal vein invasion where only the chemotherapeutic drugs are injected into the feeding vessels of the tumor with no subsequent embolization of the feeding vessels.
In order to select a modality which would produce better outcomes in advanced HCC patients (BCLC C), this study was planned.
Read the detailed description
- Aim of the study: To see the efficacy of transarterial chemotherapy in prolonging the survival of patients with unresectable HCC when compared to oral chemotherapy 2. Diagnostic criteria
- Cirrhosis of liver- Diagnosis will be founded on the basis of clinical, biochemical, imaging and endoscopy findings.
- Hepatocellular carcinoma- when any one of the following is present
- Two imaging modalities (dual phase CT (DPCT)/ contrast enhanced MRI) showing arterialization of the hepatic mass
- Alpha feto protein (AFP) more than 400ng/ml along with arterialization on one imaging modality (DPCT/ contrast enhanced MRI)
- Fine-needle aspiration cytology (FNAC)
- Definitions
3.1. Unresectable HCC- • Liver mass larger than 5cm in diameter (single/ multiple) , involving main portal vein with underlying cirrhotic liver
3.2. Tumor response This will be based on Dual phase CT findings
- Complete response (CR)- Tumor fully covered with lipiodol showing no viable tissue
- Partial response (PR)- Tumor partially covered (>75%) by lipiodol
- Mild response (MR)- About 50 to 75% coverage of the tumor by lipiodol
- No response (NR) - About 25 to 50% coverage of the tumor by lipiodol
- Fresh lesions (FL)- Appearance of new mass lesions in the liver with or without recurrence at the site of previous mass
3.3 Patient tolerance Grade 1: no side effects Grade 2: moderate side effects Grade 3: severe side effects Grade 4: life threatening side effects
3.4 Performance status (PST score) PST score of 0-5 would be assessed on the following basis 0- No cancer related symptoms. Normal life style
- Minor symptoms related to cancer. Capable of non-strenuous activity. Fully ambulatory
- Ambulatory and capable of all self-care but unable to carry out any work activities. Confined to bed less than 50% of waking hours
- Capable of only limited self-care. Confined to bed more than 50% of waking hours.
- Completely disabled. Cannot carry on any self-care. Totally confined to bed.
- Death
- Sample Size Systematic review of RCT's for TAC show a 2-year survival of 40 %. Expecting that oral chemotherapy has a 2-year survival of 40% with 5% non-inferiority margin with 80% power and 5% error, a sample size of 124 patients in each arm would be required.(Total 248 patients)
- Randomization
- Patients will be randomized after the confirmation of diagnosis and obtaining written consent
- Sequences will be generated by the Statistician
- Stratified randomization will be done. Two strata of child's A and B will be made
- Randomization will be done by drawing consecutively numbered opaque sealed envelopes Randomization into A (TAC) and B (oral chemotherapy) will be done
- Follow up post TAC
6.1 Clinical follow up
- All patients would be followed up in the Liver clinic monthly unless their clinical condition warrants earlier follow up
- Liver function tests/ complete blood count would also be done at each visit and AFP (if elevated earlier) every six months
- Patient tolerance, child's status would be estimated.
6.2 Imaging follow up
- At one month, a dual phase CT would be done to ascertain the response to therapy and the need to repeat the procedure. Subsequently, the DPCT would be done at 3 and 6 monthly intervals.
- Repeat TAC on follow up This would be done if any of the following is noted
- DPCT shows viable tumor
- Fresh lesions appear
- Elevated serum AFP occurs with or without appearance of viable mass on DPCT
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Transarterial chemotherapy, Oral chemotherapy
- Keywords
- Transarterial chemotherapy, Thalidomide, Capecitabine
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transarterial chemotherapyProcedure or surgery
Also called TAC
Femoral artery would be punctured at the upper thigh using 18 gauge needle under local anesthesia. Catheterization of the hepatic artery feeding the tumor would be done and placing the catheter tip beyond the gastroduodenal artery, the chemotherapeutic drugs would be administered.
Mixture would be prepared by using Doxorubicin 50mg and Cisplatin 100mg. Hydrocortisone 100mg and augmenting dose of analgesic and sedative would be injected prior to the administration of the drug.
The drug mixture would then be injected through the indwelling arterial catheter by continuously flushing alternately, repeatedly and rapidly between two-leur lock syringes.
Oral chemotherapyDrug
Also called OC
Drugs used would be Thalidomide and Capecitabine in the following dosage schedule- Thalidomide---50mg once a day (OD) for 7 days, increased to 100mg OD for 7 days, 200mgOD for 7 days further increased to 300 mg OD.
Capecitabine---- 500mg OD for 7 days, then 1000mg OD for next 7 days, increased to a maximum dose of 1500mg OD
Maintenance dose - Capecitabine 1500 mg - every alternate week Thalidomide - 300 mg OD. Total leucocyte count \& Platelet count would be monitored every 15 days
| Study group | Role | What they receive |
|---|---|---|
| Transarterial chemotherapy | Active comparator | Doxorubicin 50mg, Cisplatin 100mg Receives: Procedure: Transarterial chemotherapy |
| Oral chemotherapy | Placebo comparator | Thalidomide---50-300mg once a day Capecitabine---- 500-1500mg once a day Receives: Drug: Oral chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival rate-
Survival rate to be calculated from the start of Transarterial chemotherapy
Measured: 1 year
Secondary outcomes (1)
Tumor response
Tumor response on dual phase contrast-enhanced computed tomography (CECT)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2014 (estimated)
- Study startJan 2006
- Primary completionDec 2014 (estimated)
- Study completionMar 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 124 participants (estimated)
Sponsor and investigators
- Lead sponsor
- All India Institute of Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Indian Council of Medical Research
- Responsible party
- Principal investigator, Subrat Kumar Acharya, All India Institute of Medical Sciences
- Investigators
- Subrat K Acharya, D.M, Principal investigator, All India Institute of Medical Sciences, New Delhi, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02240771
- Sponsor's protocol ID
- TAC-HCC
- Status last verified
- Sep 2014
- First submitted
- 31 Aug 2014
- Last updated
- 16 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Control Trial of Transarterial Chemotherapy (TAC) Versus Oral Thalidomide and Capecitabine in the Treatment of Unresectable Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT02240771
- Acronym / sponsor ID
- TAC-HCC
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Transarterial chemotherapy, Thalidomide, Capecitabine
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 124 participants (estimated)
- Lead sponsor
- All India Institute of Medical SciencesUniversity, hospital or other
- Collaborators
- Indian Council of Medical Research
- Study start
- Jan 2006
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Mar 2015 (estimated)
- First posted
- 16 Sep 2014 (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.
In India, majority of our patients have advanced hepatocellular carcinoma (HCC) at presentation and hence are unsuitable for the available curative treatment options. In such patients the treatment options are mainly palliative. Transarterial chemoembolization (TACE), transarterial chemotherapy (TAC) and various forms of oral chemotherapy are the only available options currently. Many patients have more advanced disease with the involvement of branches of portal vein. This further limits the therapeutic options. According to Barcelona Clinic Liver Cancer (BCLC) staging, involvement of portal vein precludes any standard form of therapy. TAC and oral chemotherapy has been tried in this group of patients by few researchers. Which treatment (TAC or oral chemotherapy) would be better suitable for advanced stage (BCLC C) needs to be explored. However, there are no randomized controlled trials (RCT's) available.
TAC is the procedure for treating patients of HCC with portal vein invasion where only the chemotherapeutic drugs are injected into the feeding vessels of the tumor with no subsequent embolization of the feeding vessels.
In order to select a modality which would produce better outcomes in advanced HCC patients (BCLC C), this study was planned.
Detailed description
- Aim of the study: To see the efficacy of transarterial chemotherapy in prolonging the survival of patients with unresectable HCC when compared to oral chemotherapy 2. Diagnostic criteria
- Cirrhosis of liver- Diagnosis will be founded on the basis of clinical, biochemical, imaging and endoscopy findings.
- Hepatocellular carcinoma- when any one of the following is present
- Two imaging modalities (dual phase CT (DPCT)/ contrast enhanced MRI) showing arterialization of the hepatic mass
- Alpha feto protein (AFP) more than 400ng/ml along with arterialization on one imaging modality (DPCT/ contrast enhanced MRI)
- Fine-needle aspiration cytology (FNAC)
- Definitions
3.1. Unresectable HCC- • Liver mass larger than 5cm in diameter (single/ multiple) , involving main portal vein with underlying cirrhotic liver
3.2. Tumor response This will be based on Dual phase CT findings
- Complete response (CR)- Tumor fully covered with lipiodol showing no viable tissue
- Partial response (PR)- Tumor partially covered (>75%) by lipiodol
- Mild response (MR)- About 50 to 75% coverage of the tumor by lipiodol
- No response (NR) - About 25 to 50% coverage of the tumor by lipiodol
- Fresh lesions (FL)- Appearance of new mass lesions in the liver with or without recurrence at the site of previous mass
3.3 Patient tolerance Grade 1: no side effects Grade 2: moderate side effects Grade 3: severe side effects Grade 4: life threatening side effects
3.4 Performance status (PST score) PST score of 0-5 would be assessed on the following basis 0- No cancer related symptoms. Normal life style
- Minor symptoms related to cancer. Capable of non-strenuous activity. Fully ambulatory
- Ambulatory and capable of all self-care but unable to carry out any work activities. Confined to bed less than 50% of waking hours
- Capable of only limited self-care. Confined to bed more than 50% of waking hours.
- Completely disabled. Cannot carry on any self-care. Totally confined to bed.
- Death
- Sample Size Systematic review of RCT's for TAC show a 2-year survival of 40 %. Expecting that oral chemotherapy has a 2-year survival of 40% with 5% non-inferiority margin with 80% power and 5% error, a sample size of 124 patients in each arm would be required.(Total 248 patients)
- Randomization
- Patients will be randomized after the confirmation of diagnosis and obtaining written consent
- Sequences will be generated by the Statistician
- Stratified randomization will be done. Two strata of child's A and B will be made
- Randomization will be done by drawing consecutively numbered opaque sealed envelopes Randomization into A (TAC) and B (oral chemotherapy) will be done
- Follow up post TAC
6.1 Clinical follow up
- All patients would be followed up in the Liver clinic monthly unless their clinical condition warrants earlier follow up
- Liver function tests/ complete blood count would also be done at each visit and AFP (if elevated earlier) every six months
- Patient tolerance, child's status would be estimated.
6.2 Imaging follow up
- At one month, a dual phase CT would be done to ascertain the response to therapy and the need to repeat the procedure. Subsequently, the DPCT would be done at 3 and 6 monthly intervals.
- Repeat TAC on follow up This would be done if any of the following is noted
- DPCT shows viable tumor
- Fresh lesions appear
- Elevated serum AFP occurs with or without appearance of viable mass on DPCT
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transarterial chemotherapy | Active comparator | Procedure: Transarterial chemotherapyDoxorubicin 50mg, Cisplatin 100mg |
| Oral chemotherapy | Placebo comparator | Drug: Oral chemotherapyThalidomide---50-300mg once a day Capecitabine---- 500-1500mg once a day |
Who may qualify
- Ages
- 12 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Patients above 12 years of age with performance status (PST) score of 0-2
- Unresectable HCC with underlying Child's A/B cirrhosis
- Blocked Main portal vein
- No history of drug allergy
- Informed written consent of patient.
Key exclusion criteria (6 listed)
- Child's C cirrhosis
- Performance status 3-5
- Extra hepatic disease
- Co-morbid illness like coronary artery disease, congestive heart failure, chronic renal failure etc
- Previous history of encephalopathy/ upper gastrointestinal bleed in the last six months
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 |
|---|---|---|
| Transarterial chemotherapyAlso: TACFemoral artery would be punctured at the upper thigh using 18 gauge needle under local anesthesia. Catheterization of the hepatic artery feeding the tumor would be done and placing the catheter tip beyond the gastroduodenal artery, the chemotherapeutic drugs would be administered. Mixture would be prepared by using Doxorubicin 50mg and Cisplatin 100mg. Hydrocortisone 100mg and augmenting dose of analgesic and sedative would be injected prior to the administration of the drug. The drug mixture would then be injected through the indwelling arterial catheter by continuously flushing alternately, repeatedly and rapidly between two-leur lock syringes. | Procedure or surgery | Transarterial chemotherapy |
| Oral chemotherapyAlso: OCDrugs used would be Thalidomide and Capecitabine in the following dosage schedule- Thalidomide---50mg once a day (OD) for 7 days, increased to 100mg OD for 7 days, 200mgOD for 7 days further increased to 300 mg OD. Capecitabine---- 500mg OD for 7 days, then 1000mg OD for next 7 days, increased to a maximum dose of 1500mg OD Maintenance dose - Capecitabine 1500 mg - every alternate week Thalidomide - 300 mg OD. Total leucocyte count \& Platelet count would be monitored every 15 days | Drug | Oral chemotherapy |
Primary outcome
Survival rate-
Time frame: 1 year
Survival rate to be calculated from the start of Transarterial chemotherapy
1 secondary outcome
Tumor response
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2014.
Related trials for Hepatocellular Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
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.
Subrat K Acharya, D.M principal investigator
All India Institute of Medical Sciences, New Delhi, India
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Transarterial chemotherapy and Oral chemotherapy in people with Hepatocellular Carcinoma, run by All India Institute of Medical Sciences at 1 site in India.
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 5 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 16 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival rate- (time frame: 1 year). 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 16 Sep 2014; AzTrials last refreshed its copy on 8 Nov 2026.