Hepatocellular Carcinoma, Invasion, Metastasis
Conditions
Keywords
hepatocellular carcinoma, colchicine
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.
Interventions
DRUGColchicine
Adjustment the dosage of colchicine during study: The colchicine dosage will be changed when the hepatic reserved function of the participant changes from Child A to B according as following: 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. If the hepatic reserved function of the participant changes to Child C, colchicine will be stopped and participant receives regular follow-up only.If participant suffers from severe diarrhea, colchicine will be temporarily stopped. When the symptom of diarrhea subsides, colchicine will be given again but the dose will be reduced 0.5 mg/day.
Sponsors
Kaohsiung Medical University Chung-Ho Memorial Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
opeo labeled
Eligibility
Sex/Gender
ALL
Age
20 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. . 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. 2. . Contrast-enhanced computed tomography or magnetic resonance imaging has evidence of distant metastasis or large vessel invasion caused by hepatocellular carcinoma. 3. . Patient has Child A hepatic reserved function
Exclusion criteria
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 must receive long-term medication of statin or fibrates drugs and these medications can not be changed. 5. . Patient has white blood cell count \< 1500/µL, platelet count \< 30000/µL or hemoglobin \< 9.0 gm/dL after medication. 6. . Pregnant woman or plan to be a pregnant woman 7. . allergy to colchicine or has history of severe side effects caused by colchicine 8. . Patient has received systemic chemotherapy within 2 months before enrollment or plans to receive systemic chemotherapy in the future. 9. . Patient is under or plans to receive Nexavar or other clinical trial testing drug. 10. . Patient has severe malfunction of vital organs and can not participate in this study justified by the doctor in this research team. 11. . Patient is under or plans to receive Chinese traditional medicine or herb drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Taiwan
Participant flow
Recruitment details
from 2013-6-6 to 2019-5-31 in Kaohsiung Medical University Hospital total 15 participants were included for screening, one screening failure, 14 participants received colchicine management
Pre-assignment details
one screening failure dut to active gastrointestinal hemorrhage
Participants by arm
| Arm | Count |
|---|---|
| Colchicine Treated Patients This group included participants receiving total daily colchicine dose equal or larger than 1.5 mg for more than 8 cycles (28 days). | 9 |
| Sorafenib Treated Group This group was originated from review of hepatocellular carcinoma patients (from January 1, 2014 to May 31, 2019) with the same condition as this trial selected participants and treated by sorafenib for more than 2 months by the research team. | 86 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 4 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Colchicine Treated Patients | Total | Sorafenib Treated Group |
|---|---|---|---|
| Age, Continuous | 60 years | 62 years | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 95 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 95 Participants | 86 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Taiwan | 9 Participants | 95 Participants | 86 Participants |
| Sex: Female, Male sex Female | 1 Participants | 20 Participants | 19 Participants |
| Sex: Female, Male sex Male | 8 Participants | 75 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 13 / 14 | 81 / 86 |
| other Total, other adverse events | 14 / 14 | 74 / 86 |
| serious Total, serious adverse events | 10 / 14 | 33 / 86 |
Outcome results
Primary
Overall Survival
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.
Time frame: up to 72 months
Population: median survival
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Colchicine Group | Overall Survival | 333 days |
| Sorafenib Treated Group | Overall Survival | 290 days |
p-value: 0.4593Mann-Whitney U test
p-value: 0.329Log Rank
Secondary
Grade III Severe Adverse Events
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.
Time frame: up to 72 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Colchicine Group | Grade III Severe Adverse Events | Diarrhea | 1 participants |
| Colchicine Group | Grade III Severe Adverse Events | Anorexia | 1 participants |
| Colchicine Group | Grade III Severe Adverse Events | Biliary tract obstruction | 2 participants |
| Colchicine Group | Grade III Severe Adverse Events | Abdominal pain | 1 participants |
| Colchicine Group | Grade III Severe Adverse Events | Hypoglycemia | 1 participants |
| Colchicine Group | Grade III Severe Adverse Events | Pneumonia | 3 participants |
| Colchicine Group | Grade III Severe Adverse Events | Peritonitis | 2 participants |
| Colchicine Group | Grade III Severe Adverse Events | Cholangitis | 2 participants |
| Colchicine Group | Grade III Severe Adverse Events | Sepsis | 0 participants |
| Colchicine Group | Grade III Severe Adverse Events | Skin rash | 0 participants |
| Colchicine Group | Grade III Severe Adverse Events | Palmar-plantar erythrodysesthesia syndrome | 0 participants |
| Colchicine Group | Grade III Severe Adverse Events | Hypertension | 0 participants |
| Colchicine Group | Grade III Severe Adverse Events | Hemorrhage | 0 participants |
| Colchicine Group | Grade III Severe Adverse Events | Hyperglycemia | 0 participants |
| Colchicine Group | Grade III Severe Adverse Events | Hypocalcemia | 0 participants |
| Colchicine Group | Grade III Severe Adverse Events | Pleural effusion | 0 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Pleural effusion | 1 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Diarrhea | 4 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Sepsis | 2 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Anorexia | 0 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Hemorrhage | 8 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Biliary tract obstruction | 0 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Skin rash | 1 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Abdominal pain | 3 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Hypocalcemia | 1 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Hypoglycemia | 0 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Palmar-plantar erythrodysesthesia syndrome | 4 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Pneumonia | 4 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Hyperglycemia | 1 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Peritonitis | 1 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Hypertension | 2 participants |
| Sorafenib Treated Group | Grade III Severe Adverse Events | Cholangitis | 2 participants |
Comparison: Comparison the incidence of grade III adverse event of pneumonia between two groupsp-value: 0.0552Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of biliary tract obstruction between two groupsp-value: 0.0184Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of cholangitis between two groupsp-value: 0.0931Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of peritonitis between two groupsp-value: 0.0506Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of sepsis between two groupsp-value: 1Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of diarrhea between two groupsp-value: 0.5374Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of anorexia between two groupsp-value: 0.14Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of abdominal pain between two groupsp-value: 0.4584Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of skin rash between two groupsp-value: 1Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of palmar-plantar erythrodysesthesia syndrome between two groupsp-value: 1Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of hypertension between two groupsp-value: 1Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of hemorrhage between two groupsp-value: 0.5958Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of hypoglycemia between two groupsp-value: 0.14Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of hyperglycemia between two groupsp-value: 1Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of hypocalcemia between two groupsp-value: 1Fisher Exact
Comparison: Comparison the incidence of grade III adverse event of pleural effusion between two groupsp-value: 1Fisher Exact