DC Vaccine in Colorectal Cancer

Phase 1

Terminated

• Conditions: Colorectal Cancer
• Interventions: Biological: DC vaccine

• Registration Number: NCT03730948
• Lead Sponsor: University of Pennsylvania

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2018-10-30
• Study First Submitted QC: 2018-11-02
• Study First Posted: 2018-11-05
• Study Start: 2019-03-12
• Primary Completion: 2022-02-22
• Study Completion: 2022-12-01
• Results First Submitted: 2024-02-19
• Status Verified: 2024-04
• Results First Submitted QC: 2024-04-29
• Last Update Submitted: 2024-04-29
• Results First Posted: 2024-05-24
• Last Update Posted: 2024-05-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All subjects	DC vaccine	All subjects will receive the vaccine and be followed per the schedule of procedures.

Primary Outcome Measures

Name	Time	Method
Changes in Numbers of Peptide-specific CD8+ T Cells (Post-vaccine Immune Response)	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.	Assessment of cellular immune activity may occur via the application of flow cytometry. Numbers of peptide-specific CD8+ T cells will be measured by flow cytometric-based intracellular cytokine or tetramer staining. Flow cytometric assays will include an examination of the influence of immunotherapy on the ability of subject T cells to exhibit phenotypic markers associated with cytolytic potential (e.g. IFN-y, IL-2, TNF-alpha, Granzyme B) after short-term stimulation by mutated peptide and p-HLA multimer staining. PBMC responses against a pool of known antigenic Cytomegalovirus, Epstein Barr Virus and Influenza epitopes will be evaluated in order to track general cellular immune competence during the study.
Adverse Events Experienced by Subjects (i.e. Safety of DC Vaccine in Subjects With Surgically Resected Hypermutated CRC)	Through study completion (at 12 months)	Number of subjects who experienced adverse events. Detailed adverse event data is presented in the AE section.

Secondary Outcome Measures

Name	Time	Method
Percentage of CD8+ Cells in Primary Tumor Tissue	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.	Descriptive models

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States