Treatment of Unresectable Hepatocellular Cancer With Opioid Growth Factor

• Status: Completed
• Trial end date: 2013-07-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Penn State University; University of Missouri-Columbia
• Collaborator: Penn State University
• Treatments: Analgesics, Opioid; Enkephalin, Methionine; Enkephalins; Mitogens

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 central nervous system (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 international normalized ratio (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

• Blood urea nitrogen (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