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

Primary Purpose

Hepatocellular Carcinoma

Status
Withdrawn
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Baclofen
Sponsored by
University of Manitoba
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular Carcinoma, GABAergic Activity, Baclofen

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Liver Unit, Section of Hepatology, Department of Medicine,Health Sciences Centre
  • Liver Unit, health sciences Centre

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
June 27, 2007
Last Updated
May 15, 2014
Sponsor
University of Manitoba
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1. Study Identification

Unique Protocol Identification Number
NCT00493428
Brief Title
Treatment of Non-Metastatic Hepatocellular Carcinoma in Humans by Increasing Gabaergic Activity: A Pilot Study
Official Title
Treatment of Non-Metastatic Hepatocellular Carcinoma in Humans by Increasing Gabaergic Activity: A Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2014
Overall Recruitment Status
Withdrawn
Why Stopped
The study have been stoped because the protocol is going to be modify.
Study Start Date
July 2007 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Manitoba

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Hepatocellular Carcinoma, GABAergic Activity, Baclofen

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Baclofen
Other Intervention Name(s)
Lioresal,Nu-Baclo
Intervention Description
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.
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Minuk Y Minuk, MD, FRCPC
Organizational Affiliation
University of Manitoba
Official's Role
Principal Investigator
Facility Information:
Facility Name
Liver Unit, Section of Hepatology, Department of Medicine,Health Sciences Centre
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 3P4
Country
Canada
Facility Name
Liver Unit, health sciences Centre
City
Winnipeg
State/Province
Manitoba
Country
Canada

12. IPD Sharing Statement

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

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