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

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ClinicalTrials.gov Identifier: NCT04846933
Recruitment Status : Recruiting
First Posted : April 15, 2021
Last Update Posted : May 10, 2021
Sponsor:
Collaborator:
University of Helsinki
Information provided by (Responsible Party):
Turku University Hospital

Brief Summary:

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, 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.

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.


Condition or disease Intervention/treatment
High Grade Ovarian Serous Adenocarcinoma Genetic: WGS and RNA sequencing Genetic: circulating tumor DNA (ctDNA) Diagnostic Test: FDG PET/CT imaging

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 cultures from cancer patients in clinical care.

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Actual Study Start Date : February 1, 2012
Estimated Primary Completion Date : December 2027
Estimated Study Completion Date : December 2029


Group/Cohort Intervention/treatment
HGSOC patients treated with Neoadjuvant chemotherapy (NACT)

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.

Genetic: WGS and RNA sequencing
Genetic: circulating tumor DNA (ctDNA)
Diagnostic Test: FDG PET/CT imaging
HGSOC patients treated with primary debulking surgery (PDS)
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.
Genetic: WGS and RNA sequencing
Genetic: circulating tumor DNA (ctDNA)



Primary Outcome Measures :
  1. Successful clinical translation [ Time Frame: 5 years ]
    The magnitude of successful clinical translation is measured by the number of times project-derived personalized medicine has impacted patients care by application of novel and existing biomarkers and therapies.

  2. Successful prediction of patient outcome with AI methods [ Time Frame: 5 years ]
    Proportion of patients whose disease outcome (PFS, OS) is predicted correctly with digital histopathology images, genomic data and routine laboratory values


Secondary Outcome Measures :
  1. Successful validation of potentially druggable genetic alterations [ Time Frame: 5 years ]
    Number of potentially druggable genetic alterations found and validated with in-vitro methods

  2. Successful prediction of genomic features from tumor histology [ Time Frame: 5 years ]
    Number of genomic features that can be successfully recognized from tumor histology

  3. Prediction of primary treatment response from tumor histology using H&E stained whole slide images and AI-based methods [ Time Frame: 5 years ]
    Number of patients whose outcome (primary therapy outcome, PFS) is predicted correctly

  4. Establishment of an updated version of Chemoresponse score (CRS) for measuring histological effect in tumor tissue after chemotherapy [ Time Frame: 5 years ]
    Predictive power of the updated CRS at interval surgery is compared with traditional CRS


Biospecimen Retention:   Samples With DNA
Tumor tissue (Fresh frozen tissue, FFPE), Whole blood samples, plasma, white cells


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
High grade serous ovarian cancer patients diagnosed at theTurku University Central Hospital who give their informed consent
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04846933


Contacts
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Contact: Johanna Hynninen +358 50 5383554 johanna.hynninen@utu.fi
Contact: Sampsa Hautaniemi +358503364765 sampsa.hautaniemi@helsinki.fi

Locations
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Finland
Turku University Hospital Recruiting
Turku, Finland, 20520
Contact: Johanna Hynninen    0505383554    johanna.hynninen@utu.fi   
Principal Investigator: Johanna Hynninen, MD, PhD         
Sponsors and Collaborators
Turku University Hospital
University of Helsinki
Investigators
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Study Director: Sampsa Hautaniemi, DTech, Prof University of Helsinki
Principal Investigator: Johanna Hynninen, MD, PhD Turku University Hospital
Additional Information:
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Responsible Party: Turku University Hospital
ClinicalTrials.gov Identifier: NCT04846933    
Other Study ID Numbers: TO7/003/21
965193 ( Other Grant/Funding Number: EU HORIZON 2020 )
First Posted: April 15, 2021    Key Record Dates
Last Update Posted: May 10, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Turku University Hospital:
chemoresistance
personalized medicine
WGS
ctDNA
digital pathology
FDG PET/CT
bioinformatics
AI
ovarian cancer
Additional relevant MeSH terms:
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Cystadenocarcinoma, Serous
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous