Effect of Colchicine for the Palliative Management of Hepatocellular Carcinoma

Phase 2

Completed

Conditions: Hepatocellular Carcinoma
Metastasis
Invasion

Interventions: Drug: Colchicine

Registration Number: NCT01935700

Lead Sponsor: Kaohsiung Medical University Chung-Ho Memorial Hospital

Brief Summary: This trial is to evaluate the potential of colchicine for the palliative management of hepatocellular carcinoma patients with distant metastasis or large vessel invasion using the Department of Health R.O.C. approved doses and methods of administration.

Detailed Description: Dosing schedule: 2 tablets (1 mg) three times per day (after breakfast, lunch and dinner); continue 4 days and stop for 3 days (1 cycle)

Adjustment the dosage of colchicine during study:

1. The colchicine dosage will be changed when the hepatic reserved function of the participant changes from Child A to B according to the following rules.

1. 2 tablets after breakfast, 1 tablet after lunch and 2 tablets after dinner; continue 4 days and stop for 3 days (1 cycle); repeat this cycle until patients quit this trial

2. If the hepatic reserved function of the participant returns to Child A, The dosage for Child A will be restored.

3. If the hepatic reserved function of the participant changes to Child C, colchicine will be stopped and participant receives regular follow-up only.

2. If participant suffers from severe diarrhea, colchicine will be temporarily stopped. When the symptom of diarrhea subsides, colchicine will be given again according to the following rules.

1. For participant receives﹝2 tablets after breakfast, 2 tablet after lunch and 2 tablets after dinner﹞, the dosage of colchicine will be changes to﹝2 tablets after breakfast, 1 tablet after lunch and 2 tablets after dinner﹞.

If diarrhea attacks again, the dosage of colchicine will be changes to﹝2 tablets after breakfast and 2 tablets after dinner﹞.

If diarrhea attacks again, the dosage of colchicine will be changes to﹝2 tablets after breakfast, 1 tablet after dinner﹞.

If diarrhea also attacks again, colchicine will be stopped and participant receives regular follow-up only.

2. For participant receives﹝2 tablets after breakfast, 1 tablet after lunch and 2 tablets after dinner﹞, the dosage of colchicine will be changes to﹝2 tablets after breakfast and 2 tablets after dinner﹞.

If diarrhea attacks again, the dosage of colchicine will be changes to﹝2 tablets after breakfast, 1 tablet after dinner﹞.

If diarrhea also attacks again, colchicine will be stopped and participant receives regular follow-up only.

3. If the participant has one of the following conditions, colchicine will be temporarily stopped. When the condition of the participant improves, colchicine will be given again after the judgment from the doctor of the research team. For participants unable to receive colchicine again, they will receive regular follow-up only.

1. There are life-threatening hemorrhage including gastrointestinal hemorrhage and hemorrhage from other vital organs such as lungs or brain.

2. . There are life-threatening bacterial, fungal or viral infection (not included hepatitis B and C virus).

3. . Patient has serum creatinine level \> 1.5 mg/dL.

4. . Patient has white blood cell count \< 1500/µL, platelet count \< 30000/µL or hemoglobin \< 9.0 gm/dL after medication.

5. The research team decides that the participant is not suitable to continue the study caused by abnormality of any vital organ or severe side effects caused by the study.

4. Colchicine will be temporarily stopped one day before transcatheter arterial chemoembolization until participant has body temperature \< 38 ℃, same hepatic reserved function as before, and serum creatinine level \< 1.5 mg/d after embolization.

Follow-up procedures and items for the participants to co-operate:

All participants will be followed according to the guide line of the National Health Council and the clinical practice in the treatment of hepatocellular carcinoma. Contrasted-enhanced computed tomography or magnetic resonance imaging will be performed within every 3 to 4 months. Serum alpha-fetoprotein will be determined at least one session within every 2 to 3 months in patients with elevated serum alpha-fetoprotein levels. The hepatic and renal function will be determined at least one session every month. The participants are asked to visit our outpatient clinic at least one session every month.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

Inclusion Criteria

. Patient has at least one of the following criteria: (1) positive for hepatocellular carcinoma evidenced by cytology or pathology, (2) serum alpha-fetoprotein level > 400 ng/mL and has evidence of hepatocellular carcinoma provided by contrast-enhanced computed tomography or magnetic resonance imaging.
. Contrast-enhanced computed tomography or magnetic resonance imaging has evidence of distant metastasis or large vessel invasion caused by hepatocellular carcinoma.
. Patient has Child A hepatic reserved function

Exclusion Criteria

. There are life-threatening hemorrhage including gastrointestinal hemorrhage and hemorrhage from other vital organs such as lungs or brain.
. There are life-threatening bacterial, fungal or viral infection (not included hepatitis B and C virus).
. Patient has serum creatinine level > 1.5 mg/dL.
. Patient must receive long-term medication of statin or fibrates drugs and these medications can not be changed.
. Patient has white blood cell count < 1500/µL, platelet count < 30000/µL or hemoglobin < 9.0 gm/dL after medication.
. Pregnant woman or plan to be a pregnant woman
. allergy to colchicine or has history of severe side effects caused by colchicine
. Patient has received systemic chemotherapy within 2 months before enrollment or plans to receive systemic chemotherapy in the future.
. Patient is under or plans to receive Nexavar or other clinical trial testing drug.
. Patient has severe malfunction of vital organs and can not participate in this study justified by the doctor in this research team.
. Patient is under or plans to receive Chinese traditional medicine or herb drugs.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
colchicine treated patients	Colchicine	2 tablets (0.5 mg/tablet) of colchicine three times per day (after breakfast, lunch and dinner); continue 4 days and stop for 3 days (1 cycle); repeat this cycle until patients quit this trial

Primary Outcome Measures

Name	Time	Method
Overall Survival	up to 72 months	The overall survival of the participants calculated from the date of enrollment to the date of death will be compared with the control group with the same TNM and the Barcelona Clinic Liver Cancer (BCLC) staging collected from 2005/1/1 to the end of this study. The overall survival of the control group was calculated from the date of receiving sorafenib treatment to the date of death.

Secondary Outcome Measures

Name	Time	Method
Grade III Severe Adverse Events	up to 72 months	The type and frequency of grade III severe adverse events based on the Common Terminology Criteria for Adverse Events (CTCAE) noted during the study period.