Treatment of Non-Metastatic Hepatocellular Carcinoma in Humans by Increasing Gabaergic Activity: A Pilot Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00493428
Recruitment Status : Withdrawn (The study have been stoped because the protocol is going to be modify.)
First Posted : June 28, 2007
Last Update Posted : May 16, 2014
Information provided by:
University of Manitoba

Brief Summary:
Recent studies indicate that liver cancer cells possess a receptor called the GABA-B receptor that when activated, inhibits the spread of cancer cells in test tubes. One of the drugs that activate these receptors is Baclofen, an agent that was originally developed to treat patients with various neurologic disorders. In this study, patients with recently identified liver cancer will be treated with Baclofen in an attempt to prevent or delay spread of the cancer beyond the liver. The time it takes for liver cancer to spread in the patients will be compared to the results obtained from patients enrolled in previous studies where Baclofen was not used.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Baclofen Phase 2

Detailed Description:
A total of 47 consecutive patients with radiologic or histologic evidence of non metastatic liver cancer will be enrolled over a 2-4 year period. Subjects will receive oral Baclofen at the manufacturer's suggested maximal dose. Clinical, hematologic, biochemical, and radiologic features of liver function, tumor metastasis and recurrence will be monitored at regular time intervals over a 2 year treatment period. The primary study end point will be the event of interest (time to metastasis or recurrence). Secondary end points will include time to metastasis following recurrence, objective tumor responses (complete, partial and non response), response duration, survival and safety. It is hoped the results of this study will permit liver cancer patients to remain candidates for surgical resection and transplantation longer than would otherwise have been the case.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Non-Metastatic Hepatocellular Carcinoma in Humans by Increasing Gabaergic Activity: A Pilot Study
Study Start Date : July 2007
Actual Primary Completion Date : January 2011
Actual Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Baclofen

Intervention Details:
  • Drug: Baclofen
    Patients will receive an initial dose of: 5 mg tid to be increased as tolerated to a maximum dose of 20 mg qid. This dose range and schedule reflects that suggested for the drug's muscle relaxant properties in human.
    Other Name: Lioresal,Nu-Baclo

Primary Outcome Measures :
  1. Document and Compare the effects of the GABAb receptor agonist Baclofen on the time to develop tumor metastasis in patients with non-metastatic HCC at diagnosis who subsequently undergo surgical resection, ablation or chemoembolization. [ Time Frame: 6 years ]

Secondary Outcome Measures :
  1. Document and compare the effects of the GABAb receptor agonist Baclofen on changes in serum tumor markers ( alpha-fetoprotein andd CA19-9 levels) in patients with no-metastatic HCC at diagnosis. [ Time Frame: 6 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • A diagnosis of HCC and no evidence of extra-hepatic metastases on CT/MRI scan of the abdomen, CT of the chest and brain and a negative bone scan.
  • Patients undergoing local therapy (resection, ablation or chemoembolization) and those listed for liver transplantation will not be excluded from participating in the study.
  • Patients with multiple space occupying lesions within the liver (but no evidence of extra-hepatic metastases) will continue to be eligible (the distinction between regenerative nodules and multi-focal HCC versus intra-hepatic metastases can not be made with certainty by presently available techniques).
  • Karnofsky Performance Status (KPS) ≥ 60 %.
  • Age 18 years or greater.
  • Life expectancy of at least 12 weeks.
  • Concomitant Medications
  • Patients should be on stable doses of other medications (no change in dose for two weeks prior to study initiation) when entered into the study.
  • Patient consent must be obtained from all patients prior to entry into the trial.
  • Patients must be accessible for treatment and follow-up i.e. residing within reasonable geographical limits of the study site.

Exclusion Criteria:

  • Any investigational agent within a minimum of 6 weeks prior to study treatment.
  • Pregnant or lactating women; women or men of childbearing potential unless using effective contraception. Patients capable of reproduction must agree to use appropriate methods of contraception during the study and for six months afterwards. Female patients of childbearing potential must have a negative urine pregnancy test within 14 days of study enrollment.
  • Patients whose partners are pregnant.
  • Other serious illness or medical conditions which would not permit the patient to be managed according to the protocol including:

    • History of a psychiatric disorder which would impair the ability to obtain consent or follow-up tumor imaging.
    • Active uncontrolled infection.
  • Any known defect in GABA metabolism or hypersensitivity to Baclofen.
  • Patients with previous organ allograft or taking immunomodulatory drugs.
  • Renal failure not being managed by dialysis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00493428

Canada, Manitoba
Liver Unit, Section of Hepatology, Department of Medicine,Health Sciences Centre
Winnipeg, Manitoba, Canada, R3E 3P4
Liver Unit, health sciences Centre
Winnipeg, Manitoba, Canada
Sponsors and Collaborators
University of Manitoba
Principal Investigator: Minuk Y Minuk, MD, FRCPC University of Manitoba

Responsible Party: Minuk Gerald, Liver Unit, Health Sciences Centre Identifier: NCT00493428     History of Changes
Other Study ID Numbers: B2006:156
First Posted: June 28, 2007    Key Record Dates
Last Update Posted: May 16, 2014
Last Verified: May 2014

Keywords provided by University of Manitoba:
Hepatocellular Carcinoma
GABAergic Activity

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases