Treatment of Unresectable Hepatocellular Cancer With Opioid Growth Factor

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2008 by Penn State University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Penn State University
ClinicalTrials.gov Identifier:
NCT00706576
First received: June 25, 2008
Last updated: July 13, 2010
Last verified: June 2008
  Purpose

Hepatocellular cancer, one of the world's most deadly tumors, is associated with chronic liver injury and cirrhosis. With the increasing occurrence of viral hepatitis, the incidence of this cancer in the United States continues to rise. Surgical resection offers the only hope for cure; but sadly, few patients are candidates for surgery due to their liver disease. Liver transplant can be an effective treatment, but due to a scarcity of organs, most patients do not qualify for this therapy either. Patients who are not candidates for these procedures have very few therapeutic options as chemotherapy and radiation have little efficacy. New therapies are desperately needed.

Opioid Growth Factor (OGF) inhibits the growth of a number of cancer lines in vitro by a receptor-mediated mechanism. In pancreatic cancer this phenomenon has been well defined not only in vitro but in animal models. Based upon these findings, a phase I trial has been conducted demonstrating that OGF can be administered safely to patients with pancreatic cancer. The investigators hypothesize that administration of OGF will inhibit the course of cancer progression in human subjects with unresectable hepatocellular cancer and cirrhosis. As a first step in testing this hypothesis, the investigators propose a phase I trial to study the toxicity and pharmacokinetics of this therapy in patients suffering from inoperable hepatocellular cancer and cirrhosis.


Condition Intervention Phase
Hepatocellular Cancer
Drug: [Met5]-enkephalin (Infusion of opioid growth factor )
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Unresectable Hepatocellular Cancer With Opioid Growth Factor: a Phase I Study

Resource links provided by NLM:


Further study details as provided by Penn State University:

Primary Outcome Measures:
  • primary outcome variable is toxicity and or tolerance to opioid growth factor in patients with hepatocellular cancer [ Time Frame: Over the period of infusion and 1 hour after infusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Study the biological kinetics and metabolism of OGF by monitoring plasma OGF levels [ Time Frame: During the infusion and 1 hour after infusion ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 42
Study Start Date: June 2008
Estimated Study Completion Date: July 2011
Estimated Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: [Met5]-enkephalin (Infusion of opioid growth factor )
    Volunteers will be treated with an intravenous infusion of opioid growth factor(OGF) starting at 100 µg/kg with a 50 µg/kg dose escalation with each succeeding group. The investigational drug, OGF, will be diluted in sterile saline to its appropriate concentration based upon the body weight of the volunteer and administered in a volume of 60 ml over 45 minutes (rate of 2 ml/min)
    Other Names:
    • OGF
    • [Met5]-enkephalin
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • In this acute dose-finding section of the study, we will enroll patients with HCC and cirrhosis.
  • Both male and female patients 18 years of age or older will be eligible.
  • Patients with cancer must have a Karnofsky performance rating of at least 50%.
  • Patients must have HCC and cirrhosis that is not amenable to current therapies including liver resection, tumor ablation, or liver transplant.
  • Patients must be mentally alert and able to give informed consent.
  • Female patients who are menopausal, or of childbearing age who are surgically sterile or practicing birth control (chemical or mechanical) are eligible.
  • All females of childbearing potential must have a serum pregnancy test upon entry into the study and must take precautions to not become pregnant during the study (from the time of enrollment until 1 week after the infusion of OGF). No corticosteroid or narcotic therapy 24 hrs prior to infusion.
  • Volunteers must refrain from alcoholic beverages for 24 hours before, and 24 hours after, the day of infusion.
  • If patients have received sorafenib, at least 4 weeks must pass from the last dose.
  • At least four weeks must pass from significant surgery and the subject must be physically recovered.

Exclusion Criteria:

  • Patients with asthma, chronic obstructive pulmonary disease, unstable cardiovascular diseases (congestive heart failure, symptoms of coronary artery disease, cardiac arrhythmias, poorly controlled hypertension, have suffered a myocardial infarction in the preceding year or have an abnormal EKG) will not be allowed.
  • Patients with poorly controlled diabetes, seizure disorders, primary CNS tumors or known brain metastases are excluded.
  • A clinical judgment will be made based on the other criteria and performance status as to the patient's ability to tolerate therapy.
  • Serum total bilirubin and INR will be used as markers of liver function in the exclusion criteria as defined in Table 1 (see below).
  • Pregnant or nursing women are not eligible.
  • Patients requiring antibiotics in the preceding week for a serious infection are not eligible.
  • Volunteers may have on the morning of the study one 8 ounce glass of water or juice and toast.
  • EKG and laboratory tests will be reviewed to evaluate whether any exclusion criteria are met.
  • Those who are not eligible will be notified.

Table 1: Exclusion Criteria

  • Leukocyte Count < 3500/μl
  • Hemoglobin < 8500/μl
  • BUN > 30mg/dl (hydrated)
  • Creatinine > 2 mg/dl
  • Platlet Count < 55,000/mm3
  • INR (unless on coumadin) > 2
  • Total Bilirubin > 3.5mg/dl
  • Sodium < 130 mmol/L
  • Potassium <3.2 mmol/L
  • Glucose > 300 or < 60 mg/dl
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00706576

Contacts
Contact: Eric T Kimchi, MD 717-531-5965 ext 5965 ekimchi@psu.edu
Contact: Kevin F Staveley-O'Carroll, MD, PhD 717-531-5965 ext 5965 ksoc@psu.edu

Locations
United States, Pennsylvania
Penn State Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Eric T Kimchi, MD    717-531-5965 ext 5965    ekimchi@psu.edu   
Contact: Kevin F Staveley-O'Carroll, MD, PhD    717-531-5965 ext 5965    ksoc@psu.edu   
Principal Investigator: Eric T Kimchi, MD         
Sub-Investigator: Kevin F Staveley-O'Carroll, MD, PhD         
Sub-Investigator: Niraj J Gusani, MD         
Sub-Investigator: Yixing Jiang, MD, PhD         
Sub-Investigator: Jill Smith, MD         
Sub-Investigator: Ian Schreibman, MD         
Sub-Investigator: Harold Harvey, MD         
Sub-Investigator: Peter Waybill, MD         
Sub-Investigator: Ian Zagon, PhD         
Sponsors and Collaborators
Penn State University
Investigators
Principal Investigator: Eric T Kimchi, MD Penn State College of Medicine
  More Information

No publications provided

Responsible Party: Eric T. Kimchi, MD, Penn State College of Medicine
ClinicalTrials.gov Identifier: NCT00706576     History of Changes
Other Study ID Numbers: 26336
Study First Received: June 25, 2008
Last Updated: July 13, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Penn State University:
Hepatocellular cancer
HCC
Opioid growth factor
OGF
Cirrhosis

Additional relevant MeSH terms:
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Mitogens
Enkephalins
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014