DC Vaccine in Colorectal Cancer

Study Overview
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Brief Summary
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This is a pilot study to assess the safety and tolerability, as well as the immune response rate, of mDC3 vaccine in patients with colorectal cancer.

Detailed Description
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This is a pilot study to assess the safety and tolerability, as well as the immune response rate, of mDC3 vaccine in patients with colorectal cancer. Eligible patients that provide written informed consent will undergo apheresis to collect blood mononuclear cells for vaccine production approximately 1 week prior to vaccine infusion. Each study subject will receive cyclophosphamide 300mg/m^2 intravenously 3 to 4 days prior to the vaccine dose to deplete regulatory T cells. For each vaccine dose, all subjects will receive autologous dendritic cells pulsed with mutated peptides. On Day 1, the subject will receive the primer vaccine dose; this will be followed by one booster vaccine dose approximately 8 weeks later. Peripheral blood will be taken weekly, and a second apheresis procedure will be performed at the end of study to monitor the immune response to the vaccine. Information will be gathered from usual clinic visits for approximately 1 year following the End of Treatment Study Visit to evaluate for disease progression.

Official Title
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Pilot Study of Mature Dendritic Cell Vaccination for Resected Hypermutated Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: DC vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically-confirmed stage I and II hypermutated colorectal cancer (CRC) Surgically resected disease Male or female patients 18+ years of age ECOG performance status 0-1 Certain laboratory values, performed within 14 days prior to consent Subjects of reproductive potential must agree to use a medically accepted birth control method during the trial and for at least two months following the trial. Provide written informed consent Exclusion Criteria: Prior malignancy within 3 years that may put subject at risk Pregnant or nursing women Concurrent treatment with systemic immunosuppressants including corticosteroids, calcineurin inhibitors, antiproliferative agents within 2 weeks of consent. Local (inhaled or topical) steroids or replacement dose prednisone are permitted. Known allergy to eggs Any uncontrolled intercurrent illness or active ongoing infection thta may put subject at additional risk

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All subjects<br>All subjects will receive the vaccine and be followed per the schedule of procedures. | Biological: DC vaccine<br>* DC vaccine for colorectal cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in numbers of peptide-specific CD8+ T cells (post-vaccine immune response) | Numbers of peptide-specific CD8+ T cells will be measured by flow cytometric-based intracellular cytokine or tetramer staining | Screening, Day 1, Day 43, Day 85. Also at following timepoints, which will vary by subject: 7-14 days after last vaccine; 30 days after last vaccine; every 3 months beginning 6 months since first vaccine until month 12. | 
| Adverse events experienced by subjects (i.e. safety of DC vaccine in subjects with surgically resected hypermutated CRC) | Review of adverse events experienced by subjects | Through study completion (at 12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of CD8+ cells in primary tumor tissue | Descriptive models | Screening, Day 1, Day 43, Day 85. Also at following timepoints, which will vary by subject: 7-14 days after last vaccine; 30 days after last vaccine; every 3 months beginning 6 months since first vaccine until month 12. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal cancer, cancer vaccine, dendritic cell vaccine