NCT04846933

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, 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for not_applicable

Timeline
43mo left

Started Feb 2012

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress80%
Feb 2012Dec 2029

Study Start

First participant enrolled

February 1, 2012

Completed
9.2 years until next milestone

First Submitted

Initial submission to the registry

April 12, 2021

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 15, 2021

Completed
6.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Expected
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2029

Last Updated

January 16, 2025

Status Verified

January 1, 2025

Enrollment Period

15.8 years

First QC Date

April 12, 2021

Last Update Submit

January 14, 2025

Conditions

Keywords

chemoresistancepersonalized medicineWGSctDNAdigital pathologyFDG PET/CTbioinformaticsAIovarian cancertumor evolutionartificial intelligenceorganoidDNA methylationradiomics

Outcome Measures

Primary Outcomes (2)

  • Successful clinical translation

    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.

    5 years

  • Successful prediction of patient outcome with AI methods

    Proportion of patients whose disease outcome (PFS, OS) is predicted correctly with digital histopathology images, genomic data and routine laboratory values

    5 years

Secondary Outcomes (4)

  • Successful validation of potentially druggable genetic alterations

    5 years

  • Successful prediction of genomic features from tumor histology

    5 years

  • Prediction of primary treatment response from tumor histology using H&E stained whole slide images and AI-based methods

    5 years

  • Establishment of an updated version of Chemoresponse score (CRS) for measuring histological effect in tumor tissue after chemotherapy

    5 years

Study Arms (2)

HGSOC patients treated with Neoadjuvant chemotherapy (NACT)

OTHER

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 sequencingGenetic: circulating tumor DNA (ctDNA)Diagnostic Test: FDG PET/CT imaging

HGSOC patients treated with primary debulking surgery (PDS)

OTHER

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 sequencingGenetic: circulating tumor DNA (ctDNA)Diagnostic Test: FDG PET/CT imaging

Interventions

HGSOC patients treated with Neoadjuvant chemotherapy (NACT)HGSOC patients treated with primary debulking surgery (PDS)
HGSOC patients treated with Neoadjuvant chemotherapy (NACT)HGSOC patients treated with primary debulking surgery (PDS)
FDG PET/CT imagingDIAGNOSTIC_TEST
HGSOC patients treated with Neoadjuvant chemotherapy (NACT)HGSOC patients treated with primary debulking surgery (PDS)

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Turku University Hospital

Turku, 20520, Finland

RECRUITING

Related Publications (2)

  • 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-refractory ovarian cancer. Cell Rep Med. 2025 Sep 16;6(9):102316. doi: 10.1016/j.xcrm.2025.102316. Epub 2025 Aug 29.

  • 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. 2023 Jun 12;41(6):1103-1117.e12. doi: 10.1016/j.ccell.2023.04.017. Epub 2023 May 18.

Related Links

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Whole Genome SequencingSequence Analysis, RNACirculating Tumor DNA

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNASequence AnalysisGenetic TechniquesInvestigative TechniquesCell-Free Nucleic AcidsNucleic AcidsNucleic Acids, Nucleotides, and NucleosidesDNA, NeoplasmDNA

Study Officials

  • Sampsa Hautaniemi, DTech, Prof

    University of Helsinki

    STUDY DIRECTOR
  • Johanna Hynninen, MD, PhD

    Turku University Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 12, 2021

First Posted

April 15, 2021

Study Start

February 1, 2012

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2029

Last Updated

January 16, 2025

Record last verified: 2025-01

Locations