Carcinoembryonic Antigen-loaded Dendritic Cells in Advanced Colorectal Cancer Patients

Phase 1

Completed

• Conditions: Colorectal Cancer; Liver Metastases
• Interventions: Biological: CEA-loaded dendritic cell vaccine

• Registration Number: NCT00228189
• Lead Sponsor: Radboud University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2003-12
• Study First Submitted: 2005-09-27
• Study First Submitted QC: 2005-09-27
• Study First Posted: 2005-09-28
• Status Verified: 2010-11
• Primary Completion: 2010-11
• Study Completion: 2010-11
• Last Update Submitted: 2010-11-26
• Last Update Posted: 2010-11-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	CEA-loaded dendritic cell vaccine	Dendritic cells pulsed with CEA-peptide
B	CEA-loaded dendritic cell vaccine	Dendritic cells electroporated with CEA-mRNA
C	CEA-loaded dendritic cell vaccine	Dendritic cells pulsed with CEA-peptide, in combination with oxaliplatin/capecitabine

Primary Outcome Measures

Name	Time	Method
Toxicity	During the study
immunological response against carcinoembryonic antigen and the control protein KLH	During the study

Trial Locations

Locations (1)

Radboud University Nijmegen Medical Center, dept. of Medical Oncology; 🇳🇱 Nijmegen, Netherlands