RCT Of Oral Thalidomide And Capecitabine Versus Supportive Therapy In The Treatment Of Unresectable Hepatocellular Carcinoma (BCLC D)
Aim The aim of the study is to compare the effect of Oral chemotherapeutic drugs
(Thalidomide and Capecitabine) in comparison with supportive therapy in the treatment of
advanced Hepatocellular carcinoma in a randomized controlled trial.
Setting The study would be conducted at the All India Institute of Medical Sciences, New
Delhi, a tertiary care teaching hospital, in the departments of Gastroenterology and
- 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
1. Two imaging modalities (dual phase CT (DPCT)/ contrast enhanced MRI) showing
arterialization of the hepatic mass
2. AFP more than 400ng/ml along with arterialisation on one imaging modality (DPCT/
contrast enhanced MRI)
3. Fine needle aspiration cytology (FNAC)
Advanced HCC-(BCLC D) Liver mass (solitary or multiple)with vascular involvement with any of
- extrahepatic disease
- distant metastasis
- PST score >2
Barcelona Clinic Liver Cancer (BCLS) staging is based on the BCLC classification (Llovet JM
et al. Lancet 2003). Liver cancer is staged into BCLC A- D according to this classification.
Tumor response: Based on DP contrast-enhanced computed tomography (CECT) done every 1, 3, 6
months after starting oral chemotherapy the response will be graded into the following-
Complete response (CR): Tumor resolved completely Partial response (PR): Tumor size
decreased >50% (product of 2 large diameters) Minor response (MR): Tumor size decreased 25
- 50% Stable disease (SD): Tumor size + 25% No response (NR): No change
Disease progression Fresh lesions or recurrence
Patient tolerance Grade 1: no side effects Grade 2: moderate side effects Grade 3: severe
side effects Grade 4: life threatening side effects
Performance status (PST score) PST score of 0-4 would be assessed on the following basis 0-
No cancer related symptoms. Normal life style
1. Minor symptoms related to cancer. Capable of non-strenuous activity.Fully ambulatory
and capable of all self-care but unable to carry out any work activities. Confined
to bed less than 50% of waking hours
2. Capable of only limited self-care. Confined to bed more than 50% of waking hours.
3. Completely disabled. Cannot carry on any self-care. Totally confined to bed.
Sample Size Earlier studies have shown 1-year response rate of 10% for doxorubicin and 25%
response rate for thalidomide. Combining these two drugs, 25% response rate is taken in the
oral chemotherapy group, 37 patients are needed in each group. (Total 74 pts)
- Patients will be randomized after the confirmation of diagnosis and obtaining written
- Sequences will be generated by the Statistician
- Randomization will be done by drawing consecutively numbered opaque sealed envelopes
Follow up 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 Alpha
fetoprotein (AFP) (if elevated earlier) every six months
- Patient tolerance, child's status would be estimated.
- Side effects to the drugs would be noted.
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 in the arm receiving oral chemotherapy.
Duration of follow up- one year after starting chemotherapy
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Subrat K Acharya, DM
All India Institute of Medical Sciences, New Delhi
India: Institutional Review Board
ICMR- D.O No.5/8/7/26/99-ECD-1