Trial record 10 of 16 for:    "familial cold autoinflammatory syndrome" OR "Familial Cold Autoinflammatory Syndrome"

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
NCT00203892
First received: September 12, 2005
Last updated: March 21, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Pancreatic Adenocarcinoma
Biological: modified CEA peptide (10mcg)
Biological: modified CEA peptide (100mcg)
Biological: modified CEA peptide (1000mcg)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • Maximum T Cell Response From Baseline [ Time Frame: baseline and every 4 weeks on treatment ] [ Designated as safety issue: No ]

    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. [ Time Frame: participants were followed while they were on study treatment, a median of 8 weeks ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 23
Study Start Date: April 2003
Study Completion Date: May 2012
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: CEA peptide 10mcg
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)
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.
Other Name: CAP1-6D
Experimental: B: CEA peptide 100 mcg
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)
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.
Other Name: CAP1-6D
Experimental: C: CEA peptide 1000mcg
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)
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.
Other Name: CAP1-6D

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00203892

Locations
United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
Investigators
Principal Investigator: Hedy Kindler, M.D. University of Chicago
  More Information

No publications provided

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT00203892     History of Changes
Other Study ID Numbers: 12095B
Study First Received: September 12, 2005
Results First Received: January 31, 2014
Last Updated: March 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Chicago:
Adenocarcinoma
Pancreas

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on October 23, 2014