Study of CAP1-6D in Patients With Locally Advanced or Surgically Resected Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the experimental vaccine modified CEA peptide CAP 1 -6D (mCEA) can produce an immune response in patients with pancreatic cancer who have received chemotherapy and radiation therapy.

Detailed Description
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PC has a dismal prognosis. Despite surgery, chemotherapy, and radiation, most patients with PC will die of distant metastatic disease. Peptide vaccine approaches offer an attractive potential treatment option. Since CEA is expressed in >90% of PC, it would make an attractive target for a vaccination approach. Several different vaccination approaches have been tested using CEA as a TAA. Although some investigators suggest that DC-based approaches are the most active, they are limited by the need to obtain patient-specific DCs. One attractive approach would be to add GM-CSF to the peptide to recruit endogenous DC to the site of vaccination. There are data on the use of tumor vaccines in advanced PC. Gjerertsen et al. used a K Ras peptide and GM-CSF in 48 patients with advanced PC. 50% of patients showed a peptide specific CTL response (Gjertsen, Buanes et al. 2001). Those that had an immune response had an increased overall survival, The data from phase I and II clinical trials was based on heavily pretreated patients with metastatic disease. The majority of clinical responses have been disease stabilization. The data in B cell lymphoma vaccines suggests that immune responses are more likely to be generated in minimum disease states (Bendandi, Gocke et al. 1999). For patients that have had a complete resection and treatment with adjuvant chemoradiation, and for patients with locally advanced nonresectable disease treated with standard chemoradiation, there is presently no therapy available to decrease the chance of disease reoccurrence. Our hypothesis is that immunization with a modified CEA peptide in Montanide/GM-CSF can lead to expansion of CEA-reactive CTL and result in control of CEA expressing pancreatic carcinomas.

Official Title
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A Randomized Pilot Phase II Study of Immunization With Modified CEA (CAP1-6D) Peptide In Patients With Locally Advanced Or Surgically Resected Adenocarcinoma of the Pancreas

Conditions
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Pancreatic Adenocarcinoma

Intervention / Treatment
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* Biological: modified CEA peptide (10mcg)
* Biological: modified CEA peptide (100mcg)
* Biological: modified CEA peptide (1000mcg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must express HLA-A2 Patients must have histologically or cytologically confirmed adenocarcinoma of the pancreas that expresses CEA either by IHC or serology. Patients prior chemotherapy must have been completed at least 28 days prior to the start of treatment Patients must have completely resected disease or unresectable locally advanced disease. Patients with resected disease who had a pancreaticoduodenectomy with negative margins. Patients with locally advanced disease or metastatic disease Patients must have completed 5FU based chemoradiation>4 weeks, but no more than 12 weeks prior to study registration. Age >18 years. ECOG performance status 0-1 Life expectancy greater than 3 months Patients must have normal organ and marrow function Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients who have had chemotherapy, biologic therapy, radiotherapy, or an experimental (investigational) agent within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to starting treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients may not have received a previous CEA vaccine. History of allergic reactions attributed to compounds of similar chemical or biologic composition to CEA, Montanide ISA-51, or GM-CSF. Patients must not have known autoimmune disorders (SLE, Rheumatoid Arthritis), conditions of immunosuppression (such as HIV), or treatment with immunosuppressive drugs (including oral steroids, continuous use of topical steroids, steroid inhalers). Replacement doses of steroids for patients with adrenal insufficiency are allowed. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active GI bleeding, inflammatory bowel disease or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant or breast-feeding women are excluded from this study because peptide vaccines and/or GM-CSF have an unknown effect on a fetus. Breastfeeding should be discontinued if the mother is gong to be treated on this clinical trial. Because the risk to patients with immune deficiency treated with peptide vaccine is unknown, HIV-positive patients are excluded from the study. Appropriate studies will be undertaken in patients with intrinsic immunosuppression when indicated. Patients with a currently active second malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix are not to be registered. Patients are not considered to have a currently active malignancy if they have completed therapy and have no evidence of recurrence for at least 5 years

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: CEA peptide 10mcg<br>Vaccine contained the modified CEA peptide (10mcg), Montanide ISA-51, and sargramostim (GM-CSF) 250mcg. Vaccine was administered on Day 1 of each 14 day cycle until progressive disease or dose-limiting toxicity for a maximum of 24 cycles. Vaccine administration site was the proximal thigh. | Biological: modified CEA peptide (10mcg)<br>* Vaccine contained the modified CEA peptide (10mcg), Montanide ISA-51, and sargramostim (GM-CSF) 250mcg. Vaccine was administered on Day 1 of each 14 day cycle until progressive disease or dose-limiting toxicity for a maximum of 24 cycles. Vaccine administration site was the proximal thigh.<br>* Other names: CAP1-6D;|
| Experimental: B: CEA peptide 100 mcg<br>Vaccine contained the modified CEA peptide (100mcg), Montanide ISA-51, and sargramostim (GM-CSF) 250mcg. Vaccine was administered on Day 1 of each 14 day cycle until progressive disease or dose-limiting toxicity for a maximum of 24 cycles. Vaccine administration site was the proximal thigh. | Biological: modified CEA peptide (100mcg)<br>* Vaccine contained the modified CEA peptide (100mcg), Montanide ISA-51, and sargramostim (GM-CSF) 250mcg. Vaccine was administered on Day 1 of each 14 day cycle until progressive disease or dose-limiting toxicity for a maximum of 24 cycles. Vaccine administration site was the proximal thigh.<br>* Other names: CAP1-6D;|
| Experimental: C: CEA peptide 1000mcg<br>Vaccine contained the modified CEA peptide (1000mcg), Montanide ISA-51, and sargramostim (GM-CSF) 250mcg. Vaccine was administered on Day 1 of each 14 day cycle until progressive disease or dose-limiting toxicity for a maximum of 24 cycles. Vaccine administration site was the proximal thigh. | Biological: modified CEA peptide (1000mcg)<br>* Vaccine contained the modified CEA peptide (1000mcg), Montanide ISA-51, and sargramostim (GM-CSF) 250mcg. Vaccine was administered on Day 1 of each 14 day cycle until progressive disease or dose-limiting toxicity for a maximum of 24 cycles. Vaccine administration site was the proximal thigh.<br>* Other names: CAP1-6D;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum T Cell Response From Baseline | T cell frequency (spots per 10^4 CD8+ cells) was measured by ELISPOT (Enzyme-linked immunosorbent spot) assay. Blood was collected for this assay at baseline and every 4 weeks for the first 8 cycles. After the eighth cycle, a blood sample was collected at the time of disease progression. The maximum T cell response was calculated as: peak value on treatment - baseline value. A positive value indicates an increase from baseline. | baseline and every 4 weeks on treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of Dose Limiting Toxicities of Immunization With Modified CEA (Carcinoembryonic Antigen) Peptide. | Dose-limited toxicity included Grade 2 or higher hemorrhage or allergic reaction or clinical evidence of autoimmune disease. Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v2.0. | participants were followed while they were on study treatment, a median of 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adenocarcinoma, Pancreas