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
18 Years
N/A
Both
Pancreatic Adenocarcinoma
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To determine the recommended minimal phase II peptide dose required to induce an optimal cytotoxic T lymphocyte (CTL) response.
Outcome Time Frame:
14 days
Safety Issue:
No
Principal Investigator
Hedy Kindler, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Chicago
Authority:
United States: Food and Drug Administration
Study ID:
12095B
NCT ID:
NCT00203892
Start Date:
April 2003
Completion Date:
June 2014
Related Keywords:
- Pancreatic Adenocarcinoma
- Adenocarcinoma
- Pancreas
- Adenocarcinoma
- Adenocarcinoma, Mucinous
Name | Location |
|---|---|
| The University of Chicago | Chicago, Illinois 60637 |
