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

Study Overview
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Brief Summary
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It is hypothesized that OGF biotherapy may be safely administered in combination with gemcitabine to individuals with unresectable pancreatic cancer. The study includes two aims, the first is to evaluate the safety and toxicity of the combination of OGF and gemcitabine chemotherapy. The second aim of the trial is to study the efficacy of OGF and gemcitabine when used in combination.

Detailed Description
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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.

Official Title
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OGF & Gemcitabine: Novel Treatment for Pancreatic Cancer Phase I, A Safety and Toxicity Study

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Biological: Opioid Growth Factor (OGF)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OGF & Gemcitabine<br>Opioid Growth factor 250 ug/kg IV once a week. Gemcitabine 1000 mg/m2 weekly for 7 out of 8 weeks induction then every 3 out of 4 week cycles. | Drug: Gemcitabine<br>* 1000mg/m2, IV (in the vein) over 30 minutes after treatment with OGF; first cycle is consecutive seven weeks and one week off; subsequent cycles are three weeks on and one week off.<br>* Other names: Gemzar;Biological: Opioid Growth Factor (OGF)<br>* Initial treatment is 150ug/kg (based on body weight of the patient) in a volume of 50ml sterile saline, IV (in the vein) over 45 minutes; subsequent treatments at dose of 250ug/kg<br>* Other names: [Met]5-enkephalin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression measured with CT scan |  | every 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreas, pancreatic cancer, cancer, Opioid Growth Factor, OGF, gemcitabine, chemotherapy