Evaluation the Palliative Effects of Colchicine on Primary Hepatic Malignant Tumors Unable to Receive Curative Treatment

NCT04264260 | Completed Phase 2

• 1 other identifier: KMUHIRB-F(II)-20190152
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is to evaluate the palliative effects of colchicine on primary hepatic malignancy using the Department of Health R.O.C. approved doses and methods of administration. Colchicine will be started from 2 tablets after meal twice per day (total 2 mg), adjust the dose ranging from total minimum 1.5 mg to maximum 3 mg per day based on the condition and tolerance of the participant. One cycle of treatment is defined as 4 days treatment and 3 days off. The participants will receive repeated treatment cycles till the participants quit the trial. The control group will be originated from review of (1) patients treated by members of this research team with the same condition as the trial selected participants but not included in the trial, (2) patients with same condition as the trial selected participants reported in the literatures. The primary objective is to evaluate the palliative effects of colchicine on primary hepatic malignancy unable to receive curative treatment. The primary end point is survival of the participant. The Secondary objective is to evaluate the safety of patients treated by colchicine and the secondary end point is the side effects of colchicine.

Conditions

Hepatocellular Carcinoma Stage IIIB; Cholangiocarcinoma, Intrahepatic; Cholangiocarcinoma; With Hepatocellular Carcinoma; Hepatocellular Carcinoma Stage IV

Keywords

hepatocellular carcinoma; Cholangiocarcinoma; primary hepatic malignancy; palliative treatment; colchicine

Outcome Measures

Primary Outcomes (1)

• survival

  The overall survival of the participants

  through study completion, an average of 31 months

Secondary Outcomes (1)

• serious adverse effect

  through study completion, an average of 31 months

Study Arms (1)

colchicine group

EXPERIMENTAL

The participants will receive colchicine starting from 2 tablets after meal twice per day (total 2 mg). The dose will be adjusted ranging from total minimum 1.5 mg to maximum 3 mg per day based on the condition and tolerance of the participant. One cycle of treatment is defined as 4 days treatment and 3 days off. The participants will receive repeated cycles till the participants quit the trial.

Drug: Colchicine Tablets

Interventions

Colchicine Tablets DRUG

three times or two times per day after meal with the daily total dose ranging from 1.5 to 3 mg

colchicine group

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (A). Primary hepatic malignancy including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, hepatocellular-cholangiocarcinoma, poorly differentiated or undifferentiated primary hepatic malignancy.
• Diagnosis of hepatocellular carcinoma: 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 on contrast-enhanced computed tomography or magnetic resonance imaging.
• Diagnosis of intrahepatic cholangiocarcinoma: Patient has at least one of the following criteria: (1) evidenced by cytology or pathology, (2) serum CA19-9 level \> 10 times of normal upper limit and has evidence on contrast-enhanced computed tomography or magnetic resonance imaging, and no evidence of extrahepatic original malignancy.
• Diagnosis of hepatocellular-cholangiocarcinoma: concomitantly fit at least one of the items described in (a) and (b)
• Diagnosis of poorly differentiated or undifferentiated primary hepatic malignancy: Patient fits all of the following criteria: (1) evidenced of malignancy other than hepatocellular carcinoma, intrahepatic cholangiocarcinoma or hepatocellular-cholangiocarcinoma by cytology or pathology, (2) no evidence of extrahepatic original malignancy
• (B). Primary hepatic malignant tumors unable to receive curative treatment indicate that the malignancy can not be completely eliminated by operative resection, liver transplantation or local abrasion therapy. Patient also needs to fit at least one of the following criteria: (1) evidence of distant metastasis or large vessels (intrahepatic first branch portal vein, portal main trunk, major hepatic vein or inferior vena cava) invasion, (2) unable to be controlled by transcatheter arterial chemoembolization including appearance of new rather than incompletely treated nodules within 3 months of chemoembolization, or chemoembolization fails
• (C). The performance status of the patient based on the Eastern Cooperative Oncology Group (ECOG) belongs to 0 or 1 and the calculated Child score is below 8 points.

You may not qualify if:

• life-threatening hemorrhage at the present time
• life-threatening bacterial, fungal or viral infection (not included hepatitis B and C virus) at the present time
• extrahepatic original malignancy unable to be controlled
• serum creatinine level \> 1.5 mg/dL.
• Patient must receive long-term statin or fibrates drugs. The doses of these medications can not be altered.
• 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 other clinical trial testing drug.
• Patient has severe malfunction of vital organs and can not participate in this study justified by the member of the research team.
• Patient is under or plans to receive Chinese traditional medicine or herb drugs.
• Patient is under or plans to receive hospice care.
• Patient took other clinical trial testing drug within 3 months before enrollment.
• Patient can not quit drug abuse or heavy alcohol drinking.

Sponsors & Collaborators

• Kaohsiung Medical University Chung-Ho Memorial Hospital: lead
• Kaohsiung Medical University: collaborator

Study Sites (1)

Kaohsiung Medical University Hospital

Kaohsiung City, 807, Taiwan

Location

Related Publications (12)

• Arrieta O, Rodriguez-Diaz JL, Rosas-Camargo V, Morales-Espinosa D, Ponce de Leon S, Kershenobich D, Leon-Rodriguez E. Colchicine delays the development of hepatocellular carcinoma in patients with hepatitis virus-related liver cirrhosis. Cancer. 2006 Oct 15;107(8):1852-8. doi: 10.1002/cncr.22198.

  PMID: 16967451 BACKGROUND

• Finkelstein Y, Aks SE, Hutson JR, Juurlink DN, Nguyen P, Dubnov-Raz G, Pollak U, Koren G, Bentur Y. Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol (Phila). 2010 Jun;48(5):407-14. doi: 10.3109/15563650.2010.495348.

  PMID: 20586571 BACKGROUND

• Imazio M, Bobbio M, Cecchi E, Demarie D, Demichelis B, Pomari F, Moratti M, Gaschino G, Giammaria M, Ghisio A, Belli R, Trinchero R. Colchicine in addition to conventional therapy for acute pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial. Circulation. 2005 Sep 27;112(13):2012-6. doi: 10.1161/CIRCULATIONAHA.105.542738.

  PMID: 16186437 BACKGROUND

• Kallinich T, Haffner D, Niehues T, Huss K, Lainka E, Neudorf U, Schaefer C, Stojanov S, Timmann C, Keitzer R, Ozdogan H, Ozen S. Colchicine use in children and adolescents with familial Mediterranean fever: literature review and consensus statement. Pediatrics. 2007 Feb;119(2):e474-83. doi: 10.1542/peds.2006-1434. Epub 2007 Jan 22.

  PMID: 17242135 BACKGROUND

• Leighton JA, Bay MK, Maldonado AL, Schenker S, Speeg KV. Colchicine clearance is impaired in alcoholic cirrhosis. Hepatology. 1991 Dec;14(6):1013-5.

  PMID: 1959847 BACKGROUND

• Rochdi M, Sabouraud A, Girre C, Venet R, Scherrmann JM. Pharmacokinetics and absolute bioavailability of colchicine after i.v. and oral administration in healthy human volunteers and elderly subjects. Eur J Clin Pharmacol. 1994;46(4):351-4. doi: 10.1007/BF00194404.

  PMID: 7957521 BACKGROUND

• Ferron GM, Rochdi M, Jusko WJ, Scherrmann JM. Oral absorption characteristics and pharmacokinetics of colchicine in healthy volunteers after single and multiple doses. J Clin Pharmacol. 1996 Oct;36(10):874-83. doi: 10.1002/j.1552-4604.1996.tb04753.x.

  PMID: 8930773 BACKGROUND

• Terkeltaub RA, Furst DE, Bennett K, Kook KA, Crockett RS, Davis MW. High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010 Apr;62(4):1060-8. doi: 10.1002/art.27327.

  PMID: 20131255 BACKGROUND

• Lin ZY, Wu CC, Chuang YH, Chuang WL. Anti-cancer mechanisms of clinically acceptable colchicine concentrations on hepatocellular carcinoma. Life Sci. 2013 Sep 3;93(8):323-8. doi: 10.1016/j.lfs.2013.07.002. Epub 2013 Jul 16.

  PMID: 23871804 BACKGROUND

• Wu CC, Lin ZY, Kuoc CH, Chuang WL. Clinically acceptable colchicine concentrations have potential for the palliative treatment of human cholangiocarcinoma. Kaohsiung J Med Sci. 2015 May;31(5):229-34. doi: 10.1016/j.kjms.2015.01.008. Epub 2015 Mar 10.

  PMID: 25910557 BACKGROUND

• Lin ZY, Kuo CH, Wu DC, Chuang WL. Anticancer effects of clinically acceptable colchicine concentrations on human gastric cancer cell lines. Kaohsiung J Med Sci. 2016 Feb;32(2):68-73. doi: 10.1016/j.kjms.2015.12.006. Epub 2016 Feb 2.

  PMID: 26944324 BACKGROUND

• Lin ZY, Yeh ML, Liang PC, Chen SC, Huang CF, Huang JF, Dai CY, Yu ML, Chuang WL. Phase IIb Trial for the Palliative Treatment of Patients With Primary Hepatic Malignancy Unable to Receive Curative Treatment: Efficacy of Colchicine. Kaohsiung J Med Sci. 2025 Sep 27:e70121. doi: 10.1002/kjm2.70121. Online ahead of print.

  PMID: 41014140 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Cholangiocarcinoma; Liver Neoplasms

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Zu Y Lin, MD

  Kaohsiung Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: open labeled

Study Record Dates

• First Submitted: February 2, 2020
• First Posted: February 11, 2020
• Study Start: December 24, 2019
• Primary Completion: May 30, 2025
• Study Completion: May 30, 2025
• Last Updated: September 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)