Colorectal CancerPhase 1/2NCT01885702
Dendritic Cell Vaccination in Patients With Lynch Syndrome or Colorectal Cancer With MSI
A Phase 1/2 study testing DC vaccination in people with Colorectal Cancer, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Objectives: In this Radboud University Nijmegen Medical Centre (RUNMC) initiated study our first objective is to investigate toxicity (safety and feasibility) of vaccination with frameshift-derived neoantigen-loaded DC of CRC patients with an MSI-positive CRC and persons who are known to be carrier of a germline… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- DC vaccination
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2010to Sep 2025
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- histologically documented evidence of CRC (group I) and Lynch syndrome carrier without signs of disease (group II)
- HLA-A2.1 phenotype is required
- MSI high tumor
- WBC >3.0 x 109/l, lymphocytes >0.8 x 109/l, platelets >100 x 109/l, serum crea¬tinine <150 µmol/l, serum bilirubin <25 µmol/l
- WHO performance status 0-1 (Karnofsky 100-70%)
- Age 18-75 years
- Expected adequacy of follow-up
- Written informed consent
Who cannot join
- History of malignancy in the past 5 years with the exception of adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
- Serious active infections, HbsAg or HIV positive (test only in case of high risk or clinical suspicion)
- Autoimmune diseases or organ allografts
- Concomitant use of immunosuppressive drugs
- Known allergy to shell fish
- Pregnant or lactating women
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, 6500 HB
About this study
Objectives:
In this Radboud University Nijmegen Medical Centre (RUNMC) initiated study our first objective is to investigate toxicity (safety and feasibility) of vaccination with frameshift-derived neoantigen-loaded DC of CRC patients with an MSI-positive CRC and persons who are known to be carrier of a germline MMR-gene mutation with no signs of disease yet.
Read more
The secondary objectives of the study are:
- to demonstrate that peptide-loaded DC can induce or enhance an immune response to tumor-associated antigen CEA and specific frameshift-derived neoantigens in the study population.
- to study the pathological and clinical responses, e.g. disease-free survival, determined according to the standard protocol.
Study design:
This study is a phase I/II open-label study.
Study population:
Two groups of adults will be vaccinated:
Group I) CRC patients, who are known to carry a germline MMR-gene mutation and patients with an MSI-positive CRC and yet unknown or negative MMR-gene mutation status.
Group II) persons who are known to be carrier of a germline MMR-gene mutation with no signs of disease yet. All participants need to be HLA-A2.1 positive.
Read the detailed description
Rationale of this study:
Ex vivo generated and tumor-antigen-loaded dendritic cells (DC) are currently used in clinical vaccination protocols in cancer patients. DC vaccines are safe, with minimal side effects. Evaluating more than 200 patients treated the past ten years we found that clinical responses measured in several patients directly coincide with specific cytotoxic T cell responses. The majority of studies investigated the therapeutic effects of DC vaccines in late-stage cancer patients with metastasis. In these (heavily) pretreated patients the immune system is compromised. Based on our observations that a specific immune response is indicative for a good clinical outcome we believe that the full potential of these immunostimulatory cells has to be exploited in high-risk patients with low tumor burden or in a precancerous state.
A good clinical model are carriers of a germline mutation in one of the DNA mismatch repair (MMR) genes, such as patients with Lynch syndrome (also known as Hereditary Non-Polyposis Colorectal Cancer or HNPCC). These persons have a lifetime risk of 60-80% for colorectal cancer that has developed within a few years from a precancerous adenoma. The immune system is thought to be of potential great importance as the colorectal cancer in Lynch syndrome is characterized by a strong lymphocyte infiltration, even at the stage of adenomas. In affected cancer lesions, MMR dysfunction results in frameshift mutations at short, repetitive DNA sequences referred to as microsatellites. In coding regions these mutations destroy gene function and have been demonstrated to lead to the production of neopeptides. These neopeptides are: 1) tumor specific, because frameshift mutations only occur in tumor cells and their premalignant progenitors, 2) are very similar between patients, since the same genes are affected by the mismatch repair defect and 3) immunogenic, since cytotoxic T cells (CTL) and helper T cells could be induced in vitro from blood of patients with Lynch syndrome. Similar mechanisms occur in sporadic colon cancer with MMR dysfunction, which represents about 10-15% of all colorectal 2.
Objectives:
In this Radboud University Nijmegen Medical Centre (RUNMC) initiated study our first objective is to investigate toxicity (safety and feasibility) of vaccination with frameshift-derived neoantigen-loaded DC of CRC patients with an MSI-positive CRC and persons who are known to be carrier of a germline MMR-gene mutation with no signs of disease yet.
The secondary objectives of the study are to demonstrate that peptide-loaded DC can induce or enhance an immune response to tumor-associated antigen CEA and specific frameshift-derived neoantigens in the study population. And we want to study the pathological and clinical responses, e.g. disease-free survival, determined according to the standard protocol.
Study design:
This study is a phase I/II open-label study.
Study population:
Two groups of adults will be vaccinated:
Group I) CRC patients, who are known to carry a germline MMR-gene mutation and patients with an MSI-positive CRC and yet unknown or negative MMR-gene mutation status.
Group II) persons who are known to be carrier of a germline MMR-gene mutation with no signs of disease yet. All participants need to be HLA-A2.1 positive.
Main study endpoints:
The first objective of this study is to toxicity (safety and feasibility) of vaccination with frameshift-derived neoantigen-loaded DC. This will be measured by recording of the adverse events according to the Common Terminology Criteria for Adverse Events version 3.0.
The secondary objectives of the study are to demonstrate that peptide-loaded DC can induce or enhance an immune response to tumor-associated antigen CEA and specific frameshift-derived neoantigens in the study population. Immune responses will be assessed as:
- proliferative and humoral response to KLH
- cytokine production of KLH stimulated PBMC
- tumor antigen-specific T cell responses in peripheral blood
- tumor antigen-specific T cell responses in biopsies from DTH
- cytokine production of T cells in biopsies from DTH
- cytotoxicity of T cells in biopsies from DTH
- immunohistochemical characterization of DTH infiltrating lymphocytes
The pathological and clinical responses, e.g. disease-free survival, will be determined according to the standard protocol.
- Conditions
- Colorectal Cancer
- Being tested
- DC vaccination
- Keywords
- Dendritic cell vaccination, MSI-high colorectal cancer (CRC), Vaccines, Immunotherapy, CRC, Germline MMR-gene mutation without disease criteria of CRC
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DC vaccinationBiological
DC vaccination
| Study group | Role | What they receive |
|---|---|---|
| MSI-positive CRC patients | Experimental | I) Adjuvant DC vaccinations for MSI-positive CRC patients (n=5) Receives: Biological: DC vaccination |
| Carriers of germline MMR-gene mutation | Experimental | II) Preventive DC vaccinations for carriers of germline MMR-gene mutation (n=20) withhout manifestation of CRC Receives: Biological: DC vaccination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and feasibility of vaccination with frameshift-derived neoantigen-loaded DC of CRC patients
Patients will be followed for toxicity, autoimmunity and immunological response during the study and 2 and 6 months thereafter at the outpatient clinic. Subsequently, follow up will be performed as for standard practice.
Toxicity will be assessed using the Clinical Toxicity Criteria NCI CTC version 3.0.
Measured: 5 years
Secondary outcomes (3)
To evaluate whether peptide-loaded DC can induce or enhance an immune response to tumor-associated antigen CEA and specific frameshift-derived neoantigens in the study population
Measured: 5 years
Pathological responses
Pathological evaluation: Biopsies of carcinomas and or adenomas will be taken. One will be snap frozen and stored at -80 and one will be fixed in buffered formalin, for maximum of 24 hours and processed using microwave enhanced procedures. The composition of the tissue will be evaluated using standard histology supplemented with immunohistochemistry for subsets of inflammatory cells. The amount of and composition of the inflammation will be quantified using automated and semi automated quantitative methods. Based on initial results mRNA studies on cytokines and or chemokines will be performed and in addition immunohistochemistry for receptors for these molecules.
Measured: 5 years
Clinical responses, e.g. disease-free survival, determined according to the standard protocol.
Progression-free survival is defined as the time from registration to the first recurrence of disease. Overall survival is defined as the time from registration to death. The status of disease is determined at regular intervals by taking the patients's history, physical examination, and colonoscopy. If signs or symptoms suggest disease recurrence at any site, the appropriate tests should be performed to confirm or exclude this.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2013 (estimated)
- Study startOct 2010
- Primary completionApr 2016
- Study completionSep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicoline Hoogerbrugge-van der Linden, professor, Study director, Radboud University Medical CenterJolanda IM de Vries, professor, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01885702
- Sponsor's protocol ID
- EudraCT 2008-005584-33
- Status last verified
- Apr 2024
- First submitted
- 18 Jun 2013
- Last updated
- 4 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Data will be shared in an upcoming publication.
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dendritic Cell Vaccination in Patients With Lynch Syndrome or Colorectal Cancer With MSI
- ClinicalTrials.gov ID
- NCT01885702
- Acronym / sponsor ID
- EudraCT 2008-005584-33
- Conditions
- Colorectal Cancer
- Keywords
- Dendritic cell vaccination, MSI-high colorectal cancer (CRC), Vaccines, Immunotherapy, CRC, Germline MMR-gene mutation without disease criteria of CRC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Apr 2016 (actual)
- Study completion
- Sep 2025 (estimated)
- First posted
- 25 Jun 2013 (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.
Objectives:
In this Radboud University Nijmegen Medical Centre (RUNMC) initiated study our first objective is to investigate toxicity (safety and feasibility) of vaccination with frameshift-derived neoantigen-loaded DC of CRC patients with an MSI-positive CRC and persons who are known to be carrier of a germline MMR-gene mutation with no signs of disease yet.
The secondary objectives of the study are:
- to demonstrate that peptide-loaded DC can induce or enhance an immune response to tumor-associated antigen CEA and specific frameshift-derived neoantigens in the study population.
- to study the pathological and clinical responses, e.g. disease-free survival, determined according to the standard protocol.
Study design:
This study is a phase I/II open-label study.
Study population:
Two groups of adults will be vaccinated:
Group I) CRC patients, who are known to carry a germline MMR-gene mutation and patients with an MSI-positive CRC and yet unknown or negative MMR-gene mutation status.
Group II) persons who are known to be carrier of a germline MMR-gene mutation with no signs of disease yet. All participants need to be HLA-A2.1 positive.
Detailed description
Rationale of this study:
Ex vivo generated and tumor-antigen-loaded dendritic cells (DC) are currently used in clinical vaccination protocols in cancer patients. DC vaccines are safe, with minimal side effects. Evaluating more than 200 patients treated the past ten years we found that clinical responses measured in several patients directly coincide with specific cytotoxic T cell responses. The majority of studies investigated the therapeutic effects of DC vaccines in late-stage cancer patients with metastasis. In these (heavily) pretreated patients the immune system is compromised. Based on our observations that a specific immune response is indicative for a good clinical outcome we believe that the full potential of these immunostimulatory cells has to be exploited in high-risk patients with low tumor burden or in a precancerous state.
A good clinical model are carriers of a germline mutation in one of the DNA mismatch repair (MMR) genes, such as patients with Lynch syndrome (also known as Hereditary Non-Polyposis Colorectal Cancer or HNPCC). These persons have a lifetime risk of 60-80% for colorectal cancer that has developed within a few years from a precancerous adenoma. The immune system is thought to be of potential great importance as the colorectal cancer in Lynch syndrome is characterized by a strong lymphocyte infiltration, even at the stage of adenomas. In affected cancer lesions, MMR dysfunction results in frameshift mutations at short, repetitive DNA sequences referred to as microsatellites. In coding regions these mutations destroy gene function and have been demonstrated to lead to the production of neopeptides. These neopeptides are: 1) tumor specific, because frameshift mutations only occur in tumor cells and their premalignant progenitors, 2) are very similar between patients, since the same genes are affected by the mismatch repair defect and 3) immunogenic, since cytotoxic T cells (CTL) and helper T cells could be induced in vitro from blood of patients with Lynch syndrome. Similar mechanisms occur in sporadic colon cancer with MMR dysfunction, which represents about 10-15% of all colorectal 2.
Objectives:
In this Radboud University Nijmegen Medical Centre (RUNMC) initiated study our first objective is to investigate toxicity (safety and feasibility) of vaccination with frameshift-derived neoantigen-loaded DC of CRC patients with an MSI-positive CRC and persons who are known to be carrier of a germline MMR-gene mutation with no signs of disease yet.
The secondary objectives of the study are to demonstrate that peptide-loaded DC can induce or enhance an immune response to tumor-associated antigen CEA and specific frameshift-derived neoantigens in the study population. And we want to study the pathological and clinical responses, e.g. disease-free survival, determined according to the standard protocol.
Study design:
This study is a phase I/II open-label study.
Study population:
Two groups of adults will be vaccinated:
Group I) CRC patients, who are known to carry a germline MMR-gene mutation and patients with an MSI-positive CRC and yet unknown or negative MMR-gene mutation status.
Group II) persons who are known to be carrier of a germline MMR-gene mutation with no signs of disease yet. All participants need to be HLA-A2.1 positive.
Main study endpoints:
The first objective of this study is to toxicity (safety and feasibility) of vaccination with frameshift-derived neoantigen-loaded DC. This will be measured by recording of the adverse events according to the Common Terminology Criteria for Adverse Events version 3.0.
The secondary objectives of the study are to demonstrate that peptide-loaded DC can induce or enhance an immune response to tumor-associated antigen CEA and specific frameshift-derived neoantigens in the study population. Immune responses will be assessed as:
- proliferative and humoral response to KLH
- cytokine production of KLH stimulated PBMC
- tumor antigen-specific T cell responses in peripheral blood
- tumor antigen-specific T cell responses in biopsies from DTH
- cytokine production of T cells in biopsies from DTH
- cytotoxicity of T cells in biopsies from DTH
- immunohistochemical characterization of DTH infiltrating lymphocytes
The pathological and clinical responses, e.g. disease-free survival, will be determined according to the standard protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MSI-positive CRC patients | Experimental | Biological: DC vaccinationI) Adjuvant DC vaccinations for MSI-positive CRC patients (n=5) |
| Carriers of germline MMR-gene mutation | Experimental | Biological: DC vaccinationII) Preventive DC vaccinations for carriers of germline MMR-gene mutation (n=20) withhout manifestation of CRC |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- histologically documented evidence of CRC (group I) and Lynch syndrome carrier without signs of disease (group II)
- HLA-A2.1 phenotype is required
- MSI high tumor
- WBC >3.0 x 109/l, lymphocytes >0.8 x 109/l, platelets >100 x 109/l, serum crea¬tinine <150 µmol/l, serum bilirubin <25 µmol/l
- WHO performance status 0-1 (Karnofsky 100-70%)
Key exclusion criteria (6 listed)
- History of malignancy in the past 5 years with the exception of adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
- Serious active infections, HbsAg or HIV positive (test only in case of high risk or clinical suspicion)
- Autoimmune diseases or organ allografts
- Concomitant use of immunosuppressive drugs
- Known allergy to shell fish
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 |
|---|---|---|
| DC vaccinationDC vaccination | Biological | Carriers of germline MMR-gene mutation, MSI-positive CRC patients |
Primary outcome
Safety and feasibility of vaccination with frameshift-derived neoantigen-loaded DC of CRC patients
Time frame: 5 years
Patients will be followed for toxicity, autoimmunity and immunological response during the study and 2 and 6 months thereafter at the outpatient clinic. Subsequently, follow up will be performed as for standard practice. Toxicity will be assessed using the Clinical Toxicity Criteria NCI CTC version 3.0.
3 secondary outcomes
To evaluate whether peptide-loaded DC can induce or enhance an immune response to tumor-associated antigen CEA and specific frameshift-derived neoantigens in the study population
Time frame: 5 years
Pathological responses
Time frame: 5 years
Clinical responses, e.g. disease-free survival, determined according to the standard protocol.
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2025.
- Individual participant dataSharing planned: Yes. Data will be shared in an upcoming publication.
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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.
Nicoline Hoogerbrugge-van der Linden, professor study director
Radboud University Medical Center
Jolanda IM de Vries, professor principal investigator
Radboud University Medical Center
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 DC vaccination in people with Colorectal Cancer, 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 8 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 4 Apr 2025. 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?
Results are not available in the source record.
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?
Safety and feasibility of vaccination with frameshift-derived neoantigen-loaded DC of CRC patients (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Apr 2025.