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

Turku University Hospital (TYKS)

Status: Enrolling

Conditions: High Grade Ovarian Serous Adenocarcinoma; High Grade Serous Carcinoma

Treatments: Diagnostic Test: FDG PET/CT imaging; Genetic: circulating tumor DNA (ctDNA); Genetic: WGS and RNA sequencing

Study type: Interventional

Funder types: Other

Identifiers

NCT04846933

965193 (Other Grant/Funding Number)

TO7/003/21

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

HGSOC patients treated with Neoadjuvant chemotherapy (NACT)

Other group

Description:

Diagnostic laparoscopy followed with 3-4 cycles of platinum-taxane NACT and interval debulking surgery (IDS). Treatment response is monitored with FDG PET/CT. IDS is followed by standard adjuvant therapy (ESGO/ESMO + local guidelines). Digital H\&E slides and WGS, RNAseq are obtained from performed surgeries including relapse operations/ascites drainages. Patients are followed with longitudinal ctDNA sampling.

Treatment:

Genetic: WGS and RNA sequencing

Genetic: circulating tumor DNA (ctDNA)

Diagnostic Test: FDG PET/CT imaging

HGSOC patients treated with primary debulking surgery (PDS)

Other group

Description:

PDS is followed by standard adjuvant therapy (ESGO/ESMO + local guidelines). Digital H\&E slides and WGS, RNAseq obtained from PDS and possible relapse operations/ascites drainages when performed. Patients are followed with longitudinal ctDNA sampling.

Treatment:

Genetic: WGS and RNA sequencing

Genetic: circulating tumor DNA (ctDNA)

Diagnostic Test: FDG PET/CT imaging