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

May 15, 2014 updated by: University of Manitoba

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.

Study Overview

Status

Withdrawn

Conditions

Hepatocellular Carcinoma

Intervention / Treatment

Drug: Baclofen

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

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Canada
- Manitoba
  - Winnipeg, Manitoba, Canada, R3E 3P4
    - Liver Unit, Section of Hepatology, Department of Medicine,Health Sciences Centre
  - Winnipeg, Manitoba, Canada
    - Liver Unit, health sciences Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	6 years

Secondary Outcome Measures

Outcome Measure	Time Frame
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	6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Manitoba

Investigators

Principal Investigator: Minuk Y Minuk, MD, FRCPC, University of Manitoba

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Actual)

January 1, 2011

Study Completion (Actual)

January 1, 2011

Study Registration Dates

First Submitted

June 27, 2007

First Submitted That Met QC Criteria