NEOadjuvant Dendritic Cell Vaccination for Ovarian Cancer (NEODOC)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Epithelial Ovarian Cancer; Ovarian Carcinoma
• Intervention / Treatment: Biological: XP-DC vaccinations

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Bouke Koeneman, MD; Phone Number: +31 (0)24 361 76 00; Email: bouke.koeneman@radboudumc.nl

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500 HB
      • Recruiting
      • Radboud University Medical Center
      • Contact: Bouke Koeneman, MD; Phone Number: +31243617600; Email: bouke.koeneman@radboudumc.nl
      • Contact: Nelleke Ottevanger, MD, PhD; Phone Number: +31243618800; Email: nelleke.ottevanger@radboudumc.nl
      • Principal Investigator: Jolanda de Vries, prof. dr.
      • Principal Investigator: Nelleke Ottevanger, dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Women over 18 years old with histologically confirmed primary epithelial ovarian cancer.
• Not amenable by primary debulking surgery and in need of neoadjuvant chemotherapy and interval debulking
• High-grade or low grade serous histology
• FIGO stage IIIb, IIIc, IVa or IVb if only lymph nodes ≤ 1cm above the diaphragm or in the groins
• Extensive abdominal spread of tumor
• WHO/ECOG performance status 0-1
• Neutrophils >1.5x 109/L, platelets >100x 109/L, hemoglobin >5,6 mmol/L (9.0 g/dl), estimated glomerular filtration rate > 45 ml/min/1.73m2 , AST/ALT <3 x ULN, serum bilirubin <1.5 x ULN (exception: Gilbert's syndrome is permitted)
• Expected adequacy of follow-up

• Postmenopausal or evidence of non-childbearing status or for women of childbearing potential: negative urine or serum pregnancy test, within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as:

  • Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments;
  • or surgical sterilisation (bilateral oophorectomy or hysterectomy).
• Informed consent

Exclusion criteria

• Recurrent ovarian cancer
• Histologies other than high grade serous ovarian cancer such as, but not restricted to, endometrioid, mucinous, clear cell or carcinosarcoma
• Unable and/or unwilling to undergo standard chemotherapy and interval debulking surgery
• FIGO stage I-IIb, IIIa or IVb with liver, spleen or lung metastases or lymph nodes above the diaphragm or in the groins > 1 cm
• History of any second malignancy, with the exception of adequately treated basal cell carcinoma, cervical cancer > 5 years ago or early stage breast cancer >10 years ago.
• Any serious clinical condition that may interfere with the safe administration of DC vaccinations
• Heart failure (NYHA class III/IV)
• Any uncontrolled co-morbidity, e.g. psychiatric or social conditions interfering which participation
• Unable to undergo a tumor biopsy
• Pregnancy or insufficient anti-conception if reproduction is still possible
• Active infection of Hepatitis B, C, HIV and syphilis
• Serious other active infections
• Known allergy to shell fish
• Auto immune disease (exception: vitiligo is permitted)
• History of organ allografts
• Chronic treatment with systemic immunosuppressive drugs (i.e. more than 10 mg prednisolone equivalent)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XP-DC vaccinations; Patients in this arm will receive XP-DC vaccination in addition to standard-of-care treatment.	Biological: XP-DC vaccinations; Autologous cross-presenting dendritic cells loaded with autologous tumor lysate and KLH; Other Names: dendritic cell vaccine; cdc1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with an immunological response to XP-DC vaccination	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.	At DTH skin test after the second vaccination (approximately study week 10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by incidence of treatment-related adverse events	Toxicity will be assessed according to CTCAE version 4.03.	Throughout the treatment phase until 1 year of follow-up
Recurrence free survival (RFS) after 12 months	Percentage of patients alive without recurrence of disease after 12 months	1 year
Number of patients with complete pathological response	The number of patients with a complete pathological response	At time of debulking surgery (approximately study week 11)
Feasibility of tumor lysate-loaded XP-DC vaccinations in patients with advanced EOC	Feasibility assessment will be based on reporting of: the number of patients from whom a successful apheresis product can be obtained; the number of patients from whom (both quantitatively and qualitatively) sufficient tumor lysate can be obtained; the number of patients for whom a DC product can be manufactured that meets the prespecified criteria; the number of patients that has received the planned number of vaccinations.	Throughout the treatment phase until the last planned vaccination (approximately study week 23)

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Nelleke Ottevanger, MD/PhD, Radboud University Medical Center

Publications and helpful links

General Publications

• Koeneman B, Schreibelt G, Duiveman-de Boer T, Bos K, van Oorschot T, Pots J, Scharenborg N, de Boer A, Hins-de Bree S, de Haas N, de Goede A, Westdorp H, van Ham M, de Vries IJM, Ottevanger PB. NEOadjuvant Dendritic cell therapy added to first line standard of care in advanced epithelial Ovarian Cancer (NEODOC): protocol of a first-in-human, exploratory, single-centre phase I/II trial in the Netherlands. BMJ Open. 2025 Nov 9;15(11):e102184. doi: 10.1136/bmjopen-2025-102184.

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 12, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 17, 2023

Study Record Updates

• Last Update Posted (Estimated): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: immunotherapy; ovarian cancer; dendritic cell vaccination
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Immunologic Factors; Physiological Effects of Drugs; CDC1 protein, S cerevisiae
• Other Study ID Numbers: NEODOC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD underlying the results in the publication will be made available in an online data repository under restricted access.
• IPD Sharing Time Frame: IPD will be available beginning no longer than 3 months after the publication with no end date
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No