OveRcoming immunosupprEssion aNd rebAlancing the Immune reSponSe in ovAriaN CancEr Study

Gynaecologisch Oncologisch Centrum Zuid2 个研究点分布在 1 个国家目标入组 90 人开始时间: 2025年1月1日最近更新: 2025年12月12日

适应症

试验速览

阶段: 不适用
状态: 招募中
发起方
入组人数: 90
试验地点: 2
主要终点: Cell composition of immune organs using flow cytometry

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Ovarian cancer (OC) is one of the most lethal cancers in the world due to late-stage disease at diagnosis. Standard therapy consists of debulking surgery and chemotherapy. However, despite this aggressive treatment, recurrent disease almost invariably occurs resulting in a five-year survival rate of approximately 30%.

Immunotherapy could be a way to increase survival in OC patients. However, a major barrier to a successful deployment of cancer immunotherapy for ovarian cancer patients is the immunosuppressive tumor microenvironment.

Envisioned solution/research direction

Tumor-related inflammation is one of the hallmarks of cancers in general. Innate immunity specifically is a common denominator that is involved in the pathogenesis of OC. To improve the patient's outcome and identify novel therapeutic targets, one needs a deeper understanding of the tumor-induced changes in the bone marrow myeloid progenitor cells. Furthermore, treatment of these cells by nanoparticles or other agents that induce a program of 'trained immunity' may be a novel way to re- educate myeloid cells and their bone marrow progenitors in OC patients.

Hypothesis

We hypothesize that by exposing myeloid cells or their progenitors to various agents that induce trained immunity (e.g. trained immunity-inducing agents: BCG, heat-killed Candida,), these immune cells will undergo functional reprogramming to induce a tumor-suppressive phenotype. In the future, this could be explored as a novel immunotherapy for tumors that are refractory to conventional treatment.

Objective

To characterize and phenotype the immune state of OC patients compared to controls without cancer with a focus on the hematopoietic organs and the immune cells originating from these organs. In addition, the effect of established trained immunity-inducing agents on these cells will be evaluated in vitro, potentially providing new therapies.

This will be executed by assessing the transcriptional, epigenetic, and functional reprogramming of circulating monocytes and myeloid progenitor cells in OC and by assessing the in vitro effect of trained immunity inducers on the reprogramming of circulating monocytes and myeloid progenitor cells.

Study design: investigator-initiated, multi-center explorative cross-sectional study at the Catharina hospital Eindhoven, Radboud University Medical Center and Eindhoven University of Technology.

详细描述

INTRODUCTION AND RATIONALE

Problem description/ unmet needs:

Ovarian cancer is the fifth leading cause of cancer death among women in the Western world. The high mortality rate is due to detection at an advanced stage of the disease and lack of curative therapies. Standard therapy consists of a combination of cytoreductive surgery and chemotherapy. Despite this aggressive treatment, recurrent disease almost invariably occurs resulting in a five-year survival rate of only 30%, which has not changed significantly over the last 30 years.

Recurrent ovarian cancer is generally treated with second/third line chemotherapy, and (costly) targeted therapies. Although targeted therapy options are rapidly expanding, response rates often fall short of expectations probably caused by heterogeneity of the disease. Therefore, new treatment options need to be explored. One such option is immunotherapy. However, the limited data on this topic show disappointing results.

Envisioned solution/research direction:

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Other
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: Female
接受健康志愿者: 是

入选标准

•Subjects should be at least 18 years old and mentally competent;
•Newly diagnosed patients with OC who go for primary debulking surgery or patients with OC who are scheduled for interval debulking;
•Controls: women who undergo surgery for benign gynaecological conditions under general anaesthesia.

排除标准

•Mentally incompetent;
•Pregnant or breastfeeding;
•Known inflammatory of infectious diseases or an immunosuppressive status;
•Using medication interfering with the immune system;
•Severe comorbidities: other active malignancy (except for basal cell carcinoma and other in situ carcinomas);
•Serious psychiatric pathology;
•A self reported alcohol consumption of >21 units per week.