Opioid Growth Factor (OGF) and Gemcitabine: Novel Treatment for Pancreatic Cancer

Pancreatic cancer is the 4th leading cause of cancer-related deaths in the United States with
a median survival of 3-6 months and a five-year survival rate of 1% making it the worse of
all gastrointestinal malignancies. The reason for the poor prognosis is related to failure to
diagnose this cancer in early stages and the unresponsiveness of pancreatic cancer to
conventional chemotherapy and radiation therapy. Gemcitabine has become the standard of care
in treatment of advanced pancreatic cancer; however, the mean survival with gemcitabine is
reported at only 5.6 months. Our research team has discovered a novel biotherapy called
Opioid Growth Factor (OGF) that inhibits growth of pancreatic cancer in vitro, in animals,
and in human subjects. A Phase 1 study with OGF has been completed and the maximum tolerated
dose, safety and toxicity evaluated. Currently a Phase 2 trial is in progress to study the
efficacy of OGF monotherapy in those who have not responded to standard treatment. Recent
experiments from our basic science laboratories indicate a marked additive benefit in cancer
inhibition when OGF is combined with gemcitabine. Additionally, animals receiving the
combination regime were healthier than those treated with gemcitabine alone suggesting
perhaps a protective effect of OGF to chemotherapy toxicity. It is hypothesized that OGF may
be safely administered in combination with gemcitabine to individuals with unresectable
pancreatic cancer. In order to test this hypothesis 22 eligible naïve patients with
pancreatic cancer will be prospectively treated with standard doses of gemcitabine.
Concomitantly, OGF will be administered weekly starting at 150 μg/kg and increasing to the
Maximum tolerated dose of 250 μg/kg in order to determine the following specific aims: 1)
evaluate the safety and toxicity of the combination of OGF biotherapy and gemcitabine; 2)
determine whether the combination therapy alters the pharmacokinetics of either agent; and 3)
study the efficacy of combination therapy on tumor size, patient survival, and time to
progression of disease. The long-term goal of our research team involves translation of novel
discoveries from the basic science laboratory into clinical practice with the ultimate goal
of improving survival of patients with this devastating disease.

Inclusion Criteria:

- unresectable and histological or cytological confirmation of adenocarcinoma of the
pancreas and measurable disease by CT scan

- patient has not been previously treated for pancreatic cancer

Exclusion Criteria:

- history of cancer other than pancreatic cancer (excluding resected basal cell skin
cancer or curative stage 1 cervical cancer if disease free for 5 years or more)

- previous treatment with chemotherapy for pancreatic cancer

- uncontrolled cardiovascular disease (congestive heart failure, symptoms of coronary
artery disease, cardiac arrhythmias)

- suffered from myocardial infarction in preceding 6 months

- poorly controlled medical conditions including: asthma, chronic obstructive pulmonary
disease, diabetes, seizure disorders, known brain metastases, hepatic or renal failure

- pregnant or nursing women

- known allergy to gemcitabine