Colorectal CancerPhase 1/2NCT00228189
Carcinoembryonic Antigen-loaded Dendritic Cells in Advanced Colorectal Cancer Patients
A Phase 1/2 study testing CEA-loaded dendritic cell vaccine in people with Colorectal Cancer and Liver Metastases, run by Radboud University Medical Center at 1 site in Netherlands.
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer, Liver Metastases
- What is being tested?
- CEA-loaded dendritic cell vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteNetherlands
- Study dates
- Dec 2003to Nov 2010
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- 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
- Platelets ≥ 100x109/l
- Hb ≥ 6 mmol/l
- Total bilirubin ≤ 2x UNL
- ASAT and ALAT ≤ 3x UNL
- Serum creatinine ≤ 1.5 x UNL
- Expected adequacy of follow-up
- Signed written informed consent
Who cannot join
- 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.
- A history of myocardial infarction, angina pectoris, cardiac arrhythmias, cerebrovascular accidents, transient ischemic attacks or severe hypertension (exclusion criteria for autologous blood donation)
- 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.
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- A known allergy to shell fish.
- Pregnant or lactating women.
- For arm C (side-study)
- 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
- Serious concomitant disease. Autoimmune disease or organ grafts.
- Other serious concomitant diseases preventing the safe administration of study drugs or likely to interfere with the study assessments.
- A known allergy to shell fish (contains KLH)
- Pregnant or lactating women
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Center, dept. of Medical Oncology
Nijmegen, P.O. box 9101 6500 HB
About this study
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.
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
- Being tested
- CEA-loaded dendritic cell vaccine
- Keywords
- Dendritic cells, Colorectal cancer, Carcinoembryonic antigen, Vaccine, Immunotherapy
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CEA-loaded dendritic cell vaccineBiological
Carcinoembryonic antigen (either peptide or mRNA) loaded dendritic cells.
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Dendritic cells pulsed with CEA-peptide Receives: Biological: CEA-loaded dendritic cell vaccine |
| B | Experimental | Dendritic cells electroporated with CEA-mRNA Receives: Biological: CEA-loaded dendritic cell vaccine |
| C | Experimental | Dendritic cells pulsed with CEA-peptide, in combination with oxaliplatin/capecitabine Receives: Biological: CEA-loaded dendritic cell vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
immunological response against carcinoembryonic antigen and the control protein KLH
Measured: During the study
Toxicity
Measured: During the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2005 (estimated)
- Study startDec 2003
- Primary completionNov 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Prof. dr. C.J.A. Punt, MD,PhD, Principal investigator, Radboud University Nijmegen Medical Center, dept. of Medical Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00228189
- Sponsor's protocol ID
- 920-03-250
- Other IDs
- NWO920-03-250
- Status last verified
- Nov 2010
- First submitted
- 27 Sep 2005
- Last updated
- 30 Nov 2010
- Results posted
- No
Publications
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.
PubMed 15122249Lesterhuis 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.
PubMed 18262431de 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.
PubMed 16110035Lesterhuis 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.
PubMed 16600979Lesterhuis 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.
PubMed 21187495
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00228189
- Acronym / sponsor ID
- 920-03-250
- Conditions
- Colorectal Cancer, Liver Metastases
- Keywords
- Dendritic cells, Colorectal cancer, Carcinoembryonic antigen, Vaccine, Immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Dec 2003
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 28 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Biological: CEA-loaded dendritic cell vaccineDendritic cells pulsed with CEA-peptide |
| B | Experimental | Biological: CEA-loaded dendritic cell vaccineDendritic cells electroporated with CEA-mRNA |
| C | Experimental | Biological: CEA-loaded dendritic cell vaccineDendritic cells pulsed with CEA-peptide, in combination with oxaliplatin/capecitabine |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
- A history of myocardial infarction, angina pectoris, cardiac arrhythmias, cerebrovascular accidents, transient ischemic attacks or severe hypertension (exclusion criteria for autologous blood donation)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CEA-loaded dendritic cell vaccineCarcinoembryonic antigen (either peptide or mRNA) loaded dendritic cells. | Biological | A, B, C |
Primary outcome
immunological response against carcinoembryonic antigen and the control protein KLH
Time frame: During the study
Toxicity
Time frame: During the study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2010.
- Background: PubMed 15122249Figdor 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.
- Background: PubMed 18262431Lesterhuis 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.
- Background: PubMed 16110035de 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.
- Results publication: PubMed 16600979Lesterhuis 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.
- Derived from this study: PubMed 21187495Lesterhuis 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.
- Home page of the Radboud University Nijmegen Medical CenterLink provided by the sponsor.
- Website of the tumor immunology department of the Nijmegen Center for Molecular Life Sciences of the Radboud University Nijmegen Medical CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prof. dr. C.J.A. Punt, MD,PhD principal investigator
Radboud University Nijmegen Medical Center, dept. of Medical Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CEA-loaded dendritic cell vaccine in people with Colorectal Cancer and Liver Metastases, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Nov 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
immunological response against carcinoembryonic antigen and the control protein KLH (time frame: During the study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00228189, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2010.