Clinical Research Directory

Multi-layer Data to Improve Diagnosis, Predict Therapy Resistance and Suggest Targeted Therapies in HGSOC

Chemotherapy resistance is the greatest contributor to mortality in advanced cancers and severe challenges remain in finding effective treatment modalities to cancer patients with metastasized and relapsed disease. High-grade serous ovarian cancer (HGSOC) is typically diagnosed at a stage where the disease is already widely spread to the abdomen and current standard of practice treatment consists of surgery followed by platinum-taxane based chemotherapy and maintenance therapy. While 90% of HGSOC patients show no clinically detectable signs of cancer after surgery and chemotherapy, only 43% of the patients are alive five years after diagnosis because of chemoresistant cancer. This prospective, observational trial focuses on revealing major mechanisms causing chemoresistance in HGSOG patients and derive personalized treatment regimens for chemotherapy resistant HGSOC patients. The investigators recruit newly diagnosed advanced stage HGSOC patients who are then thoroughly followed during their cancer treatment. Longitudinal sampling includes digitalized H\&E stained histology slides mainly collected during routine diagnostics, fresh tumor \& ascites samples for next-generation sequencing/proteomics (WGS, RNA-seq, DNA-methylation, ATAC-seq, ChIP-seq, mass cytometry, etc.) and ex vivo experiments, plasma samples for circulating tumor DNA (ctDNA) analyses. Broad range of clinical parameters such as laboratory and radiologic parameters (e.g., FDG PET/CT), given cancer treatments and their outcomes are collected. Radiomic analyses are performed to PET/CT and CT scans. Long-term patient derived organoid lines are established from fresh tumor tissues. Actionable genomic alterations are searched. The general objective is to establish a clinically useful precision oncology approach based on multi-level data collected in longitudinal setting, and translate the most potent and validated discoveries into clinical use. DECIDER project will produce AI-powered diagnostic tools, cutting-edge software platforms for clinical decision-making, novel data analysis \& integration methods, and high-throughput ex vivo drug screening approaches.

Combination of Olaparib and Navitoclax in Women with HGSC and TNBC

The purpose of this Phase I study is to determine if the PARP inhibitor olaparib can be safely combined with navitoclax, an inhibitor of Bcl-2/Bcl-XL, in women with TNBC who have somatic or germline mutations in breast cancer gene one (BRCA1) and breast cancer gene two (BRCA2) BRCA1/2 or PALB2 and in women with recurrent HGSC who have progressed greater than 6 months since their last platinum containing chemotherapy. The trial is designed as an open- label multi-center Phase I interventional and translational study. It will identify the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D of olaparib combined with navitoclax for study in Phase II. There is a plan for a follow on Phase II study depending on the results obtained during this Phase I trial.The rationale for this study is that for a subset of patients, olaparib, will increase tumor cell survival dependence on inhibition of cell death by Bcl 2/Bcl- XL. Thus, navitoclax will augment apoptosis induced by PARP inhibition with olaparib.

Adaptive ChemoTherapy for Ovarian Cancer in Patients With Replased Platinum-sensitive High Grade Serous or High Grade Endometrioid Ovarian Cancer

ACTOv will compare standard 3-weekly carboplatin (AUC5), to carboplatin delivered according to an AT regimen. The AT regimen will modify carboplatin dose according to changes in the clinical-standard serum biomarker CA125 as a proxy measure of total tumour burden and an individual patient's response to the most recent chemotherapy treatment. AT could prolong sensitivity to carboplatin and extend tumour control, while simultaneously reducing chemotherapy dose and drug-induced toxicity. Carboplatin is a low cost and low toxicity drug that has an enduring and central role in ovarian cancer treatment.