Transarterial Chemotherapy Compared With Oral Chemotherapy in the Treatment of Advanced Hepatocellular Carcinoma

All India Institute Of Medical Science (AIIMS)

Status and phase

Unknown

Phase 3

Phase 2

Conditions

Hepatocellular Carcinoma

Treatments

Procedure: Transarterial chemotherapy

Drug: Oral chemotherapy

Study type

Interventional

Funder types

Other

Identifiers

NCT02240771

TAC-HCC

Details and patient eligibility

About

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.

Full 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

o Cirrhosis of liver- Diagnosis will be founded on the basis of clinical, biochemical, imaging and endoscopy findings.

o 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
1. 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.
1. 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

Enrollment

124 estimated patients

Sex

All

Ages

12 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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