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

Primary Purpose

Pancreatic Adenocarcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
modified CEA peptide (10mcg)
modified CEA peptide (100mcg)
modified CEA peptide (1000mcg)
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Adenocarcinoma focused on measuring Adenocarcinoma, Pancreas

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The University of Chicago

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

A: CEA peptide 10mcg

B: CEA peptide 100 mcg

C: CEA peptide 1000mcg

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
September 12, 2005
Last Updated
March 21, 2014
Sponsor
University of Chicago
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1. Study Identification

Unique Protocol Identification Number
NCT00203892
Brief Title
Study of CAP1-6D in Patients With Locally Advanced or Surgically Resected Pancreatic Adenocarcinoma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
April 2003 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
May 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Adenocarcinoma
Keywords
Adenocarcinoma, Pancreas

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A: CEA peptide 10mcg
Arm Type
Experimental
Arm Description
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.
Arm Title
B: CEA peptide 100 mcg
Arm Type
Experimental
Arm Description
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.
Arm Title
C: CEA peptide 1000mcg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
modified CEA peptide (10mcg)
Other Intervention Name(s)
CAP1-6D
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
modified CEA peptide (100mcg)
Other Intervention Name(s)
CAP1-6D
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
modified CEA peptide (1000mcg)
Other Intervention Name(s)
CAP1-6D
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum T Cell Response From Baseline
Description
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.
Time Frame
baseline and every 4 weeks on treatment
Secondary Outcome Measure Information:
Title
Evidence of Dose Limiting Toxicities of Immunization With Modified CEA (Carcinoembryonic Antigen) Peptide.
Description
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.
Time Frame
participants were followed while they were on study treatment, a median of 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hedy Kindler, M.D.
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24829746
Citation
Geynisman DM, Zha Y, Kunnavakkam R, Aklilu M, Catenacci DV, Polite BN, Rosenbaum C, Namakydoust A, Karrison T, Gajewski TF, Kindler HL. A randomized pilot phase I study of modified carcinoembryonic antigen (CEA) peptide (CAP1-6D)/montanide/GM-CSF-vaccine in patients with pancreatic adenocarcinoma. J Immunother Cancer. 2013 Jun 27;1:8. doi: 10.1186/2051-1426-1-8. eCollection 2013.
Results Reference
derived

Learn more about this trial

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

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