NEOadjuvant Dendritic Cell Vaccination for Ovarian Cancer

Trial Title: NEOadjuvant Dendritic Cell Vaccination for Ovarian Cancer

NCT ID: NCT05773859

Condition: Epithelial Ovarian Cancer
Ovarian Carcinoma

Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Vaccines

Conditions: Keywords:
immunotherapy
dendritic cell vaccination
ovarian cancer

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: XP-DC vaccinations
Description: Autologous cross-presenting dendritic cells loaded with autologous tumor lysate and KLH
Arm group label: XP-DC vaccinations

Other name: dendritic cell vaccine

Other name: cdc1

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.

Criteria for eligibility:
Criteria:
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 serous histology - FIGO stage IIIc or FIGO stage IIIb with extensive abdominal spread - WHO/ECOG performance status 0-1 - Neutrophils >1.5x 109/L lymphocytes >0.8x 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 1) Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments or 2) 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, low-grade serous, mucinous, clear cell or carcinosarcoma - Unable and/or unwilling to undergo standard chemotherapy and interval debulking surgery - FIGO stage I-IIb, stage IIIa, stage IV - History of any second malignancy, with the exception of adequately treated basal cell carcinoma - 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)

Gender: Female

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Radboud University Medical Center

Address:
City: Nijmegen
Zip: 6500 HB
Country: Netherlands

Status: Recruiting

Contact:
Last name: Bouke Koeneman, MD

Phone: +31243617600
Email: bouke.koeneman@radboudumc.nl

Contact backup:
Last name: Nelleke Ottevanger, MD, PhD

Phone: +31243618800
Email: nelleke.ottevanger@radboudumc.nl

Investigator:
Last name: Jolanda de Vries, prof. dr.
Email: Principal Investigator

Investigator:
Last name: Nelleke Ottevanger, dr.
Email: Principal Investigator

Start date: March 17, 2023

Completion date: October 2025

Lead sponsor:
Agency: Radboud University Medical Center
Agency class: Other

Source: Radboud University Medical Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05773859