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Dendritic Cell Vaccination in Patients With Lynch Syndrome or Colorectal Cancer With MSI

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01885702
First Posted: June 25, 2013
Last Update Posted: May 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Radboud University
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer Biological: DC vaccination Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dendritic Cell Vaccination in Patients With Lynch Syndrome or Colorectal Cancer With MSI

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 25
Study Start Date: October 2010
Estimated Study Completion Date: February 2018
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MSI-positive CRC patients
I) Adjuvant DC vaccinations for MSI-positive CRC patients (n=5)
Biological: DC vaccination
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
DC vaccination

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Information from the National Library of Medicine

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


Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Investigators
Study Director: Nicoline Hoogerbrugge-van der Linden, professor Radboud University
Principal Investigator: Jolanda IM de Vries, professor Radboud University
  More Information

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01885702     History of Changes
Other Study ID Numbers: EudraCT 2008-005584-33
First Submitted: June 18, 2013
First Posted: June 25, 2013
Last Update Posted: May 31, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be shared in an upcoming publication.

Keywords provided by Radboud University:
Dendritic cell vaccination
MSI-high colorectal cancer (CRC)
Vaccines
Immunotherapy
CRC
Germline MMR-gene mutation without disease criteria of CRC

Additional relevant MeSH terms:
Colorectal Neoplasms
Colorectal Neoplasms, Hereditary Nonpolyposis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs