Carcinoembryonic Antigen-loaded Dendritic Cells in Advanced Colorectal Cancer Patients

NCT00228189 | Completed Phase 1

• 2 other identifiers: 920-03-250NWO920-03-250
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Cancer; Liver Metastases

Keywords

Dendritic cells; Colorectal cancer; Carcinoembryonic antigen; Vaccine; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• immunological response against carcinoembryonic antigen and the control protein KLH

  During the study

• Toxicity

  During the study

Study Arms (3)

A

ACTIVE COMPARATOR

Dendritic cells pulsed with CEA-peptide

Biological: CEA-loaded dendritic cell vaccine

B

EXPERIMENTAL

Dendritic cells electroporated with CEA-mRNA

Biological: CEA-loaded dendritic cell vaccine

C

EXPERIMENTAL

Dendritic cells pulsed with CEA-peptide, in combination with oxaliplatin/capecitabine

Biological: CEA-loaded dendritic cell vaccine

Interventions

CEA-loaded dendritic cell vaccine BIOLOGICAL

Carcinoembryonic antigen (either peptide or mRNA) loaded dendritic cells.

A; B; C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological documented evidence of colorectal cancer.
• Primary tumor surgically removed, recurrence(s) in the liver.
• Planned surgical excision of liver metastases.
• HLA-A2.1 phenotype according to lymphocyte HLA typing.
• Expression of CEA on primary tumor.
• ECOG performance status 0-1, life expectancy \> 3 months.
• Age 18-75 years.
• 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.
• Expected adequacy of follow-up.
• Written informed consent.

You may not qualify if:

• Clinical signs of extra hepatic metastases, in patients with a clinical suspicion of other metastases diagnostic tests should be performed to exclude this.
• Prior chemotherapy, immunotherapy, or radiotherapy within three months before planned surgical excision is allowed.
• Concomitant use of corticosteroids or other immunosuppressive agents.
• A history of any second malignancy in the past five years excluding adequately treated basal carcinoma of skin or carcinoma in situ of cervix.
• Serious concomitant disease, active infections. Specifically, patients with autoimmune disease or organ allografts and patients with a history of HBsAg or HIV are excluded.
• A known allergy to shell fish.
• Pregnant or lactating women.
• For arm C (side-study)
• histological proof of colorectal cancer
• HLA-A0201 positive
• 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)
• ≤ 8 weeks since surgical resection of primary colorectal tumor
• Age 18-75 years
• WHO performance 0-1 (Karnofsky 100-70%)
• WBC ≥ 3.0x109/l

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud University Nijmegen Medical Center, dept. of Medical Oncology

Nijmegen, P.O. box 9101 6500 HB, Netherlands

Location

Related Publications (5)

• Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way. Nat Med. 2004 May;10(5):475-80. doi: 10.1038/nm1039.

  PMID: 15122249 BACKGROUND

• 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.

  PMID: 18262431 BACKGROUND

• 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. doi: 10.1200/JCO.2005.06.478.

  PMID: 16110035 BACKGROUND

• 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 T cell responses in DTH skin tests. Ann Oncol. 2006 Jun;17(6):974-80. doi: 10.1093/annonc/mdl072. Epub 2006 Apr 6.

  PMID: 16600979 RESULT

• Lesterhuis WJ, De Vries IJ, Schreibelt G, Schuurhuis DH, Aarntzen EH, De Boer A, Scharenborg NM, Van De Rakt M, Hesselink EJ, Figdor CG, Adema GJ, Punt CJ. Immunogenicity of dendritic cells pulsed with CEA peptide or transfected with CEA mRNA for vaccination of colorectal cancer patients. Anticancer Res. 2010 Dec;30(12):5091-7.

  PMID: 21187495 DERIVED

Related 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

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Prof. dr. C.J.A. Punt, MD,PhD

  Radboud University Nijmegen Medical Center, dept. of Medical Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 27, 2005
• First Posted: September 28, 2005
• Study Start: December 1, 2003
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: November 30, 2010

Record last verified: 2010-11

Locations

NL (1)