Dendritic Cell Vaccination in Patients With Lynch Syndrome or Colorectal Cancer With MSI
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|ClinicalTrials.gov Identifier: NCT01885702|
Recruitment Status : Active, not recruiting
First Posted : June 25, 2013
Last Update Posted : March 30, 2023
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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.
This study is a phase I/II open-label study.
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.
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer||Biological: DC vaccination||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Dendritic Cell Vaccination in Patients With Lynch Syndrome or Colorectal Cancer With MSI|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||April 2016|
|Estimated Study Completion Date :||December 2023|
Experimental: MSI-positive CRC patients
I) Adjuvant DC vaccinations for MSI-positive CRC patients (n=5)
Biological: DC vaccination
Experimental: Carriers of germline MMR-gene mutation
II) Preventive DC vaccinations for carriers of germline MMR-gene mutation (n=20) withhout manifestation of CRC
Biological: DC vaccination
- 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.
- 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 ]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.
- Clinical responses, e.g. disease-free survival, determined according to the standard protocol. [ Time Frame: 5 years ]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.
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|Ages Eligible for Study:||18 Years to 75 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||Yes|
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01885702
|Radboud University Nijmegen Medical Centre|
|Nijmegen, Gelderland, Netherlands, 6500 HB|
|Study Director:||Nicoline Hoogerbrugge-van der Linden, professor||Radboud University Medical Center|
|Principal Investigator:||Jolanda IM de Vries, professor||Radboud University Medical Center|
|Responsible Party:||Radboud University Medical Center|
|Other Study ID Numbers:||
|First Posted:||June 25, 2013 Key Record Dates|
|Last Update Posted:||March 30, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||Data will be shared in an upcoming publication.|
Dendritic cell vaccination
MSI-high colorectal cancer (CRC)
Germline MMR-gene mutation without disease criteria of CRC
Colorectal Neoplasms, Hereditary Nonpolyposis
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders