A Pilot Study, Evaluating the Efficacy of Regulatory T-cell Suppression by Ontak in Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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This study is designed to determine the duration of T reg suppression in patients with metastatic pancreatic cancer receiving Ontak. The goal is to define the optimal time for future dendritic cell vaccine administration.

Detailed Description
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Despite improved insight into the epidemiology and biology, pancreatic cancer remains a significant health problem as evidenced by the disappointing survival rates associated with advanced disease. Because of its aggressive growth and early metastatic dissemination, only 20% of patients can be treated by surgery at the time of diagnosis. Furthermore, the overall 5-year survival rate of stage IV disease is < 5% [1-3] despite chemotherapy. With such a dismal outlook, it is obvious that novel treatment strategies are required. There is limited experience in the literature with the use of Ontak in the treatment of metastatic pancreatic cancer. Viehl, et al, demonstrated in a murine model of pancreatic cancer, that ontak combined with whole tumor vaccine led to a significantly increased T cell-dependent antitumor immune response, as well as an improved survival compared to controls. Our group has an active trial at Loyola evaluating the role of dendritic cell vaccine in patients with unresectable, not metastatic, pancreatic cancer. Preliminary data suggests a correlation with time to progression and restoration of Tregs following an initial decrease after the DC injection. The goal of the current proposal is to determine the time point at which the Tregs reach the nadir within four weeks of ontak injection. When this is determined, we will eventually propose administering ontak followed by DC vaccine at the nadir Treg time point for patients with unresectable pancreatic cancer

Official Title
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A Pilot Study Evaluating the Efficacy of Regulatory T-cell (T-reg) Suppression by Denileukin Diftitox (Ontak) in Metastatic Pancreatic Cancer

Conditions
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Metastatic Pancreatic Cancer

Intervention / Treatment
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* Drug: Ontak


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male patients and nonpregnant, nonlactating female patient > 18 years old Histologic diagnosis of pancreatic cancer with distant disease seen on CT or MRI with no prior chemotherapy or radiotherapy for a least 4 weeks Karnofsky performance status equal to or greater than 70% Life expectancy of at least 3 months. No uncontrolled pain No symptoms of bowel obstruction Women with child bearing potential must agree to use adequate contraceptives. If she should become pregnant she needs to inform the treating physician Ability to give informed consent Exclusion Criteria: Positive serologic testing for HIV, AIDS, human T-cell lymphotrophic virus type 1, hepatitis B, or hepatitis C. Hemoglobin <9g/dL; hematocrit <27%; platelets <100,000/ U/L without transfusion support Creatinine > 1.8 mg/dL Serum albumin < 2.0 mg/dL AST > 3X ULN; ALT > 3X ULN Bilirubin > 1.8 Uncontrolled angina, arrhythmias, bronchospasm, hypertension, or hypercalcemia. Corticosteroid use within 28 days Chemotherapy or radiation within 28 days Bacteremia or other signs of active systemic infection History of autoimmune disease

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: 1<br>Three doses of Ontak 9 mcg/Kg IV over 30 minutes every other day for 1 week | Drug: Ontak<br>* One dose of Ontak 9 mcg/Kg IV over 30 minutes times 3 doses. 1 dose every other day<br>* Other names: Denileukin diftitox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T-reg Suppression From a Fractionated Dose of Ontak in Patients With Metastatic Pancreatic Cancer | The duration of T reg suppression from a fractionated dose of Ontak in patients will be measured in patients with metastatic pancreatic cancer. | days 8, 12 ,19,26 and 33 post administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal Time for Future Dendritic Cell Vaccine Administration | The goal is to define the optimal time with 95% sensitivity and 95% specificity for future dendritic cell vaccine administration | 33 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Denileukin diftitox, Metastatic Pancreatic Cancer, Ontak, Regulatory T-cell