OTCHCC: Oral Chemotherapy Versus Supportive Therapy In The Treatment Of Unresectable Hepatocellular Carcinoma

Sponsor

All India Institute of Medical Sciences, New Delhi (Other)

Overall Status

Unknown status

CT.gov ID

NCT01438450

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background Hepatocellular carcinoma, a malignant tumour of liver is one of the most common cancers worldwide. All India Institute Of Medical Sciences (AIIMS) being a tertiary care hospital receives about two to three cases of Hepatocellular carcinoma (HCC) each day in the investigators Gastroenterology out patient department. Most of these patients present late when the disease is already advanced and no curative therapies can be offered. At this stage, palliative therapy forms the mainstay of treatment. This includes transarterial chemoembolization (TACE) or Oral chemotherapy. Many patients also have involvement of branches of portal vein, which further limit therapeutic options. According to Barcelona Clinic Liver Cancer (BCLC) staging of liver cancer, involvement of portal vein precludes any standard form of therapy. These patients have been recommended for experimental therapies. Various forms of chemotherapy have been tried this group of patients. HCC is a vascular tumour and thalidomide is an anti-angiogenic drug and inhibits vascularity and has been used in the treatment of HCC. Capecitabine is a novel drug, which gives continuous delivery of 5-FU and has been used in patients with HCC and has been found to be safe.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Oral Other: Supportive	Phase 2/Phase 3

Detailed Description

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 Radiodiagnosis.

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
AFP more than 400ng/ml along with arterialisation on one imaging modality (DPCT/ contrast enhanced MRI)
Fine needle aspiration cytology (FNAC)

Definitions

Advanced HCC-(BCLC D) Liver mass (solitary or multiple)with vascular involvement with any of the following

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

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
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.
Dead

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)

Randomization

Patients will be randomized after the confirmation of diagnosis and obtaining written consent
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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

74 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

RCT Of Oral Thalidomide And Capecitabine Versus Supportive Therapy In The Treatment Of Unresectable Hepatocellular Carcinoma (BCLC D)

Study Start Date :

Oct 1, 2007

Anticipated Primary Completion Date :

Aug 1, 2013

Anticipated Study Completion Date :

Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Supportive Supportive therapy	Other: Supportive No specific therapy will be given Other Names: Supportive therapy
Active Comparator: Oral Oral thalidomide and capecitabine	Drug: Oral Capecitabine : 500 mg OD x 1 week 500 mg BD x 1 week 500 mg (2 morning, 1 evening) x 1 week After attaining the max dose of 1500 mg, a cycle of Capecitabine 1500mg every day for 2 weeks and 1 week off to be maintained. Thalidomide: 50 mg OD x 1 week 100 mg OD x 1 week 200 mg OD x 1 week, 300 mg OD x 1 week Other Names: Oral chemotherapy

Arm

Intervention/Treatment

No Intervention: Supportive

Supportive therapy

Other: Supportive

No specific therapy will be given

Other Names:

Supportive therapy

Active Comparator: Oral

Oral thalidomide and capecitabine

Drug: Oral

Capecitabine : 500 mg OD x 1 week 500 mg BD x 1 week 500 mg (2 morning, 1 evening) x 1 week After attaining the max dose of 1500 mg, a cycle of Capecitabine 1500mg every day for 2 weeks and 1 week off to be maintained. Thalidomide: 50 mg OD x 1 week 100 mg OD x 1 week 200 mg OD x 1 week, 300 mg OD x 1 week

Other Names:

Oral chemotherapy

Outcome Measures

Primary Outcome Measures

Survival [1 year]

Secondary Outcome Measures

Tumour response [1 year]
Number of patients with side effects [1 year]
Patients developing various adverse events will be recorded
Quality of life [1 year]
Change from baseline in Child status at 1 year [1 year]
Child status is calculated from the following 5 parameters Bilirubin < 2: 1, 2-3: 2 and > 3 : 3 points Albumin: > 3.5: 1, 2.8-3.5 : 2 and <2.8: 3 points Prothrombin time( seconds over control): 1-3: 1, 4-6: 2 and > 6: 3 Encephalopathy: None: 1, (grade 1 and 2): 2 and (grade 3 and 4): 3 Ascites: Absent: 1, slight: 2 and moderate: 3 Child A: score 5-6, Child B: 7-9 and Child C: 10 or more

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients above 12 years of age with
ECOG performance status (PST) score of 3 or above
Underlying Child's A and B cirrhosis
More than 50% involvement of liver by tumor
Thrombosed main portal vein
HV/IVC thrombosis
Extra hepatic disease
Metastatic disease
Informed written consent of patient

Exclusion Criteria:

History of drug allergy
Co-morbid illness like coronary artery disease, congestive heart failure, chronic renal failure etc
Pregnancy
Outstation patients from distant areas not in a position to follow up