Carcinoembryonic Antigen-loaded Dendritic Cells in Advanced Colorectal Cancer Patients

This study has been completed.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00228189
First received: September 27, 2005
Last updated: November 26, 2010
Last verified: November 2010
  Purpose

Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. As such they are currently used in clinical vaccination protocols in cancer patients. We evaluate the ability of mature DCs pulsed with carcinoembryonic antigen (CEA)-peptide (arm A) or electroporated with CEA-mRNA (arm B) to induce CEA-specific T cell responses in patients with resectable liver metastases from colorectal cancer. To evaluate immune responses, CEA-specific T cell reactivity is monitored in peripheral blood, resected abdominal lymph nodes, tumor tissue and biopsies of vaccination sites and post-treatment DTH skin tests. Patients are vaccinated intradermally and intravenously with CEA-peptide pulsed mature DCs three times prior to resection of liver metastases. In 2007 a side-study has been added (arm C), in which patients with stage III or high-risk stage II colorectal cancer that are amenable for standard adjuvant oxaliplatin/capecitabine therapy are vaccinated with CEApeptide-pulsed DCs. Also in this group, safety and immune responses in peripheral blood and the DTH-skin test are the primary endpoints. Results are compared with the results obtained in arm A.


Condition Intervention Phase
Colorectal Cancer
Liver Metastases
Biological: CEA-loaded dendritic cell vaccine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Induction of Specific T Cell Responses in Colorectal Cancer Patients With Liver Metastases Upon Vaccination With Autologous Dendritic Cells Pulsed With CEA-peptide or Electroporated With CEA-RNA: Evaluation of in Vivo Immune Response.

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • immunological response against carcinoembryonic antigen and the control protein KLH [ Time Frame: During the study ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: During the study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: December 2003
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Dendritic cells pulsed with CEA-peptide
Biological: CEA-loaded dendritic cell vaccine
Carcinoembryonic antigen (either peptide or mRNA) loaded dendritic cells.
Experimental: B
Dendritic cells electroporated with CEA-mRNA
Biological: CEA-loaded dendritic cell vaccine
Carcinoembryonic antigen (either peptide or mRNA) loaded dendritic cells.
Experimental: C
Dendritic cells pulsed with CEA-peptide, in combination with oxaliplatin/capecitabine
Biological: CEA-loaded dendritic cell vaccine
Carcinoembryonic antigen (either peptide or mRNA) loaded dendritic cells.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

For arm A and B

Inclusion Criteria:

  1. Histological documented evidence of colorectal cancer.
  2. Primary tumor surgically removed, recurrence(s) in the liver.
  3. Planned surgical excision of liver metastases.
  4. HLA-A2.1 phenotype according to lymphocyte HLA typing.
  5. Expression of CEA on primary tumor.
  6. ECOG performance status 0-1, life expectancy > 3 months.
  7. Age 18-75 years.
  8. WBC > 3.0 x 109/l, lymphocytes > 0.8 x 109/l, platelets > 100 x 109/l, serum creatinine < 150 μmol/l, serum bilirubin < 25 μmol/l.
  9. Expected adequacy of follow-up.
  10. Written informed consent.

Exclusion Criteria:

  1. Clinical signs of extra hepatic metastases, in patients with a clinical suspicion of other metastases diagnostic tests should be performed to exclude this.
  2. Prior chemotherapy, immunotherapy, or radiotherapy within three months before planned surgical excision is allowed.
  3. A history of myocardial infarction, angina pectoris, cardiac arrhythmias, cerebrovascular accidents, transient ischemic attacks or severe hypertension (exclusion criteria for autologous blood donation)
  4. Concomitant use of corticosteroids or other immunosuppressive agents.
  5. A history of any second malignancy in the past five years excluding adequately treated basal carcinoma of skin or carcinoma in situ of cervix.
  6. Serious concomitant disease, active infections. Specifically, patients with autoimmune disease or organ allografts and patients with a history of HBsAg or HIV are excluded.
  7. A known allergy to shell fish.
  8. Pregnant or lactating women.

For arm C (side-study)

inclusion criteria:

  1. histological proof of colorectal cancer
  2. HLA-A0201 positive
  3. stage III (T1-4N1-2M0) cancer or high risk stage II (T4 and/or poor differentiation in histology and/or perforation and/or obstruction and/or venous invasion and/or histological analysis of ≤10 lymph nodes)
  4. ≤ 8 weeks since surgical resection of primary colorectal tumor
  5. Age 18-75 years
  6. WHO performance 0-1 (Karnofsky 100-70%)
  7. WBC ≥ 3.0x109/l
  8. Platelets ≥ 100x109/l
  9. Hb ≥ 6 mmol/l
  10. Total bilirubin ≤ 2x UNL
  11. ASAT and ALAT ≤ 3x UNL
  12. Serum creatinine ≤ 1.5 x UNL
  13. Expected adequacy of follow-up
  14. Signed written informed consent

exclusion criteria

  1. A history of second malignancy within the last 5 years. Adequately treated basal carcino¬ma of skin or carcinoma in situ of cervix is acceptable within this period
  2. Serious concomitant disease. Autoimmune disease or organ grafts.
  3. Other serious concomitant diseases preventing the safe administration of study drugs or likely to interfere with the study assessments.
  4. A known allergy to shell fish (contains KLH)
  5. Pregnant or lactating women
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00228189

Locations
Netherlands
Radboud University Nijmegen Medical Center, dept. of Medical Oncology
Nijmegen, Netherlands, P.O. box 9101 6500 HB
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Prof. dr. C.J.A. Punt, MD,PhD Radboud University Nijmegen Medical Center, dept. of Medical Oncology
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: C.J.A. Punt, MD, PhD, Radboud University Nijmegen Medical Centre
ClinicalTrials.gov Identifier: NCT00228189     History of Changes
Other Study ID Numbers: 920-03-250, NWO920-03-250
Study First Received: September 27, 2005
Last Updated: November 26, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
Dendritic cells
Colorectal cancer
Carcinoembryonic antigen
Vaccine
Immunotherapy

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases

ClinicalTrials.gov processed this record on August 18, 2014