Metastatic Pancreatic Cancer
Conditions
Keywords
Denileukin diftitox, Metastatic Pancreatic Cancer, Ontak, Regulatory T-cell
Brief summary
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
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
Interventions
DRUGOntak
One dose of Ontak 9 mcg/Kg IV over 30 minutes times 3 doses. 1 dose every other day
Sponsors
Riveria Country Club Organization
Eisai Inc.
Loyola University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| T-reg Suppression From a Fractionated Dose of Ontak in Patients With Metastatic Pancreatic Cancer | days 8, 12 ,19,26 and 33 post administration | The duration of T reg suppression from a fractionated dose of Ontak in patients will be measured in patients with metastatic pancreatic cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Optimal Time for Future Dendritic Cell Vaccine Administration | 33 Days | The goal is to define the optimal time with 95% sensitivity and 95% specificity for future dendritic cell vaccine administration |
Countries
United States
Participant flow
Recruitment details
Recruitment for this study began on 06/18/2008 and ended on 01/09/2012
Participants by arm
| Arm | Count |
|---|---|
| Ontak Three doses of Ontak 9 mcg/Kg IV over 30 minutes every other day for 1 week | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Ontak |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
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.
Time frame: days 8, 12 ,19,26 and 33 post administration
Population: Zero participants were analyzed, because the manufacturer withdrew support for the study due to a drug supply interruption
Secondary
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
Time frame: 33 Days
Population: Zero participants were analyzed, because the manufacturer withdrew support for the study due to a drug supply interruption