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

NCT01885702 | Active Not Recruiting Phase 1

• 1 other identifier: EudraCT 2008-005584-33
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Colorectal Cancer

Keywords

Dendritic cell vaccination; MSI-high colorectal cancer (CRC); Vaccines; Immunotherapy; CRC; Germline MMR-gene mutation without disease criteria of CRC

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  5 years

• Pathological responses

  5 years

• Clinical responses, e.g. disease-free survival, determined according to the standard protocol.

  5 years

Study Arms (2)

MSI-positive CRC patients

EXPERIMENTAL

I) Adjuvant DC vaccinations for MSI-positive CRC patients (n=5)

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

Biological: DC vaccination

Interventions

DC vaccination BIOLOGICAL

DC vaccination

Carriers of germline MMR-gene mutation; MSI-positive CRC patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Nicoline Hoogerbrugge-van der Linden, professor

  Radboud University Medical Center

  STUDY DIRECTOR

• Jolanda IM de Vries, professor

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2013
• First Posted: June 25, 2013
• Study Start: October 1, 2010
• Primary Completion: April 1, 2016
• Study Completion: September 1, 2025
• Last Updated: April 4, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)