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Preventive Dendritic Cell Vaccination for Lynch Syndrome Carriers

ConditionLynch Syndrome
Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age35-75
SponsorRadboud University Medical Center

About this trial

The primary objective is to assess the effect of vaccination with neopeptide-loaded dendritic cells on disease-free survival (DFS) compared to placebo in LS subjects who are known to be carrier of a germline MMR-gene mutation with no signs of disease.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

a confirmed gPV in MLH1 or MSH2 and without a prior history of MMR-D cancer.

a confirmed gPV in MSH6, whether or not they have a history of MMR-D cancer. MSH6 subjects with a history of MMR-D cancer have to be cancer-free for more than 1 year.

previous surgical treatment may include any resection up to and including hemicolectomy; subjects who have undergone (sub)total colectomy are excluded due to the substantially reduced risk of cancer occurrence.

aged between 35 and 75 for subjects with gPV in MLH1 and MSH2; and aged between 40 and 75 for subjects with gPV in MSH6.

Disqualifiers

Individuals with a history of malignancy in the past. Allowed malignancies are adequately treated basal cell carcinoma and squamous cell carcinoma of the skin, carcinoma in situ (e.g., DCIS/LCIS/cervical CIS), papillary thyroid carcinoma, and low-risk prostate carcinoma; all locally resected with negative surgical margins and not treated with systemic therapy.

Organ allografts.

Known allergy to shellfish.

Inability to understand and communicate in Dutch.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Arm A: DC vaccination

    Biological/Vaccine

    Subjects in the DC vaccination arm will receive a maximum of 2 cycles each consisting of 3 DC injections intranodally (3-7x10\^6 DC)

  • Arm B: Placebo vaccination

    Biological/Vaccine

    Subjects in the placeb vaccination arm will receive a maximum of 2 cycles each consisting of 3 placebo injections intranodally (3-7x10\^6 DC)

Treatment groups

372 Participants
are divided into 2 treatment groups
Group A: Arm A: DC vaccinationExperimental treatment 1 intervention
Group B: Arm B: Placebo vaccinationPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Disease-free survival after DC vaccination or placebo

Defined as time between 1st vaccination until development of mismatch-repair deficient colorectal adenoma, any Lynch-related carcinoma in situ or Lynch-related carcinoma, Lynch-related death, or until follow-up ends, whichever occurs first.

Time frame
58.5 months

Secondary outcomes

1

Number of participants with Treatment-Related adverse events as assessed by CTCAE v5.0 (Safety)

Time frame
36 months
2

Quality of Life Questionnaires

To evaluate whether LS subjects quality of life differs between DC vaccinated and placebo vaccinated groups. Defined as patient's self-perceived physical, psychological and social well-being in relation to their health status, assessed using questionnaires.

Time frame
baseline, week 3, week 28, month 12, month 24, month 36, month 48
3

To assess whether neoantigen-specific T cells are induced by the DC vaccine (immunogenicity).

Immunogenicity will be assessed by the percentage of participants showing a neo-antigen-specific T cell response, defined by the expansion of T cells that recognize tumor antigens and demonstrate effector functions. Non-responders are those with no T cell expansion or insufficient immune activity.

Time frame
36 months
4

Health economic aspects including QALY

The primary objective of the analysis is to determine the cost-effectiveness of DC vaccination compared with standard surveillance in patients with LS, expressed as cost per quality-adjusted life year (QALY) gained and incremental net monetary benefit (iNMB) from a societal perspective, over both the trial timeframe (empirical) and the long term timeframe (modelling).

Time frame
58.5 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Radboud University Medical Center

Lead sponsor

Dutch National Health Care Institute

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: