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

Official title

Integration of Multiple Data Levels to Improve Diagnosis, Predict Treatment Response and Suggest Targets to Overcome Therapy Resistance in High-grade Serous Ovarian Cancer

Overview

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.

Detailed description

Specific aims include:

* Develop tools and methods for personalized medicine approaches to cancer patients. * Develop open-source visualization and interpretation software that facilitate clinical decision making via data integration and interpretation of multilevel data from cancer patients. * Rapidly identify HGSOC patients who are likely to respond poorly to current therapies combining information on digitalized histopathology samples, genomic and clinical data with AI methods. * Deploy validated personalized medicine treatment options using longitudinal measurement and ex vivo organoid cultures from cancer patients in clinical care.

Interventions

• Genetic WGS and RNA sequencing
• Genetic circulating tumor DNA (ctDNA)
• Diagnostic test FDG PET/CT imaging

Primary outcome measures

• Successful clinical translation [Time frame: 5 years]
• Successful prediction of patient outcome with AI methods [Time frame: 5 years]

Secondary outcome measures (4)

• Successful validation of potentially druggable genetic alterations [Time frame: 5 years]
• Successful prediction of genomic features from tumor histology [Time frame: 5 years]
• Prediction of primary treatment response from tumor histology using H&E stained whole slide images and AI-based methods [Time frame: 5 years]
• Establishment of an updated version of Chemoresponse score (CRS) for measuring histological effect in tumor tissue after chemotherapy [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Patients with a suspected ovarian cancer diagnosis treated at the Turku University Hospital
• Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

• Age <18 years, too poor condition for active treatment (surgery, chemotherapy)
• FDG PET/CT scan is not performed for patients with diabetes mellitus and poor glucose balance.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

Finland · 1 center

• Turku University Hospital — Turku

Publications

• Afenteva D, Yu R, Rajavuori A, Salvadores M, Launonen IM, Lavikka K, Zhang K, Pirttikoski A, Marchi G, Jamalzadeh S, Isoviita VM, Li Y, Micoli G, Erkan EP, Falco MM, Ungureanu D, Lahtinen A, Oikkonen J, Hietanen S, Vaharautio A, Sur I, Virtanen A, Farkkila A, Hynninen J, Muranen TA, Taipale J, Hautaniemi S. Multi-omics analysis reveals the attenuation of the interferon pathway as a driver of chemo PMID 40885189
• Lahtinen A, Lavikka K, Virtanen A, Li Y, Jamalzadeh S, Skorda A, Lauridsen AR, Zhang K, Marchi G, Isoviita VM, Ariotta V, Lehtonen O, Muranen TA, Huhtinen K, Carpen O, Hietanen S, Senkowski W, Kallunki T, Hakkinen A, Hynninen J, Oikkonen J, Hautaniemi S. Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma. Cancer Cell. PMID 37207655

Identifiers

NCT: NCT04846933 · TO7/003/21 · 965193

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗