Induction of Neo-Antigen Specific Cytotoxic T Cells by Autologous Tumor Lysate-loaded Specialized Cross-Presenting Dendritic Cells in Epithelial Ovarian Cancer Patients Treated With Neoadjuvant Chemotherapy, the NEODOC Study
Overview
- Phase
- Phase 1
- Intervention
- XP-DC vaccinations
- Conditions
- Epithelial Ovarian Cancer
- Sponsor
- Radboud University Medical Center
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Number of patients with an immunological response to XP-DC vaccination
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
This goal of this single arm, single center, exploratory phase I/II clinical trial is to learn more about the immunological efficacy, safety and feasibility of an autologous tumor lysate-loaded autologous XP-DC (cDC1)-based vaccine in patients with ovarian cancer.
Detailed Description
Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Despite intensified treatment, 5-year overall survival rates only improved modestly over the last 20 years and remain low at around 30% for patients with advanced disease in the Netherlands. To this day, results from trials with the checkpoint inhibitors, that have revolutionized treatment in other cancer types, have been disappointing in EOC. Therefore, novel effective therapies are long awaited. Recently, naturally circulating blood -derived dendritic cells (nDC) were shown to be potent in inducing cytotoxic immune responses and tumor regression in cancer patients. An even more specialized DC subset, referred to as cDC1 (conventional Dendritic Cells type 1) or XP-DC (specialized cross presenting DC) have shown their superiority in preclinical models. They are better at inducing cytotoxic T-cell responses against tumors after uptake of necrotic tumor cell material, a phenomenon called cross-presentation. This capability in cross-presentation makes XP-DC an ideal DC type in combination with tumor lysate-loading to induce immune responses against the scarce neoantigens present in EOC tumors. The objective of this exploratory trial is to investigate the immunological efficacy as well as safety and feasibility of tumor-lysate loaded XP-DC in EOC patients undergoing (neo-)adjuvant chemotherapy. To this end 10 patients with stage III ovarian cancer will be included and offered a combined approach with DC vaccination in addition to standard-of-care chemotherapy and surgery. Extensive monitoring of the immune system throughout the course of the trial will be performed.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
XP-DC vaccinations
Patients in this arm will receive XP-DC vaccination in addition to standard-of-care treatment.
Intervention: XP-DC vaccinations
Outcomes
Primary Outcomes
Number of patients with an immunological response to XP-DC vaccination
Time Frame: At DTH skin test after the second vaccination (approximately study week 10)
Immunologically responding patients are defined as: T cells isolated from vaccine challenged sites (DTH biopsies) that can be expanded and 1) express T cell receptors specific for the vaccine and 2) show effector functions measured by IFN-gamma secretion or cytolytic activity against tumor antigen expressing target cells. Immunologically non-responding patients are defined as: No T cells, or T cells isolated from DTH biopsies that cannot be expanded, or T cells that can be expanded but do not recognize tumor antigens, or can recognize tumor antigens but do not display T effector functions i.e. lysis of tumor cell targets or release of IFN-α.
Secondary Outcomes
- Safety as assessed by incidence of treatment-related adverse events(Throughout the treatment phase until 1 year of follow-up)
- Feasibility of tumor lysate-loaded XP-DC vaccinations in patients with advanced EOC(Throughout the treatment phase until the last planned vaccination (approximately study week 23))
- Recurrence free survival (RFS) after 12 months(1 year)
- Number of patients with complete pathological response(At time of debulking surgery (approximately study week 11))