Carcinoembryonic Antigen-loaded Dendritic Cells in Advanced Colorectal Cancer Patients

Colorectal Cancer Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00228189
• Other study ID #: 920-03-250
• Secondary ID: NWO920-03-250
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 27, 2005
• Last updated: November 26, 2010
• Start date: December 2003
• Est. completion date: November 2010

Study information

• Verified date: November 2010
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Liver Metastases
• Liver Neoplasms
• Neoplasm Metastasis

Intervention

Biological:
• CEA-loaded dendritic cell vaccine
Carcinoembryonic antigen (either peptide or mRNA) loaded dendritic cells.

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Center, dept. of Medical Oncology	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (4)

de Vries IJ, Bernsen MR, Lesterhuis WJ, Scharenborg NM, Strijk SP, Gerritsen MJ, Ruiter DJ, Figdor CG, Punt CJ, Adema GJ. Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome. J Clin Oncol. 2005 Aug 20;23(24):5779-87. — View Citation

Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way. Nat Med. 2004 May;10(5):475-80. Review. — View Citation

Lesterhuis WJ, Aarntzen EH, De Vries IJ, Schuurhuis DH, Figdor CG, Adema GJ, Punt CJ. Dendritic cell vaccines in melanoma: from promise to proof? Crit Rev Oncol Hematol. 2008 May;66(2):118-34. doi: 10.1016/j.critrevonc.2007.12.007. Epub 2008 Feb 8. Review. — View Citation

Lesterhuis WJ, de Vries IJ, Schuurhuis DH, Boullart AC, Jacobs JF, de Boer AJ, Scharenborg NM, Brouwer HM, van de Rakt MW, Figdor CG, Ruers TJ, Adema GJ, Punt CJ. Vaccination of colorectal cancer patients with CEA-loaded dendritic cells: antigen-specific — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	immunological response against carcinoembryonic antigen and the control protein KLH		During the study	No
Primary	Toxicity		During the study	Yes

External Links

•   Home page of the Radboud University Nijmegen Medical Center
•   Website of the tumor immunology department of the Nijmegen Center for Molecular Life Sciences of the Radboud University Nijmegen Medical Center