OVASARC: CINSARC Genomic Signature as Predictor of Resectability of Ovarian Adenocarcinoma
Study Details
Study Description
Brief Summary
The majority of primary cancers of the ovary or peritoneum are represented by high-grade serous adenocarcinomas. These are rare pathologies, the incidence of which is estimated at 7.1 per 100,000, representing approximately 4,500 new cases per year in France (INCA 2017). In the absence of effective screening, nearly 85% of patients have an advanced disease at diagnosis (corresponding to the FIGO III or IVA stage, characterized by diffuse peritoneal involvement). Despite multidisciplinary care, the majority of patients (80%) will recur within a median of 18 to 24 months.
It is therefore necessary to develop new tools, in particular molecular, in order to allow :
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to better select patients accessible to full interval surgery
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to exclude patients who would not benefit from this surgery in terms of survival
In 2010, Chibon et al. identified, from a cohort of patients with soft tissue sarcoma (STM), a molecular signature (called CINSARC), based on the expression profile of 67 genes involved in mitotic control and chromosomal integrity. The team showed that this transcriptomic signature is an independent prognostic factor in different types of STM, but also a prognostic factor more discriminating than the histological grade (FNCLCC), historical and major prognostic factor of STM.
Being initially made from frozen material and on a DNA biochip (Affymetrix), this signature was unusable outside the field of fundamental research. This is why CINSARC has been gradually optimized, first by the RNA sequencing technique on frozen tissue fixed in formalin (FFPE), and recently on FFPE tissue by the NanoString® technique. This very sensitive and inexpensive technique requires only small amounts of total RNA, making it compatible with use on "routine" diagnostic samples, microbiopsy or surgical biopsy, opening the door to real clinical application. Several clinical studies using this latest CINSARC optimization (called NanoCind®) to determine the treatment of patients with STM will also begin soon.
As a result of this work, necessary in order to more precisely support the potential of CINSARC in this pathology, the investigators hope to be able to assess from the diagnosis the evolutionary potential of the patients, which could make it possible to evaluate therapeutic strategies adapted to the profiles of each subpopulation: the investigators can for example imagine in theory a therapeutic de-escalation for low-risk patients, or else, for very high-risk patients, an intensified strategy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
RNA extraction from 150 patients archival tumor, fragments of 50 to 300 nucleotides size.
RNA preparation, hybridation, detection, scanning according to Nanostring manufacturer recommandations: obtention of CINSARC molecular signature Sensibility, specificity, prognostic value of the signature will be analyzed
Study Design
Outcome Measures
Primary Outcome Measures
- The main endpoint is the sensitivity of the CINSARC signature to identify surgical resectability after neoadjuvant chemotherapy. [sept 2019-sept 2020]
Sensitivity (Se), is defined by the proportion of subjects defined as Low risk by the CINSARC signature and having been resected, among the subjects having been resected
Secondary Outcome Measures
- Specificity of the CINSARC signature [sept 2019-sept 2020]
Proportion of subjects defined as high risk by the signature and having not been resected among patients having not been resected
- Positive predictive value of the signature [sept 2019-sept 2020]
Proportion of subjects defined as Low risk by the signature among all subjects
- Negative predictive value of the signature [sept 2019-sept 2020]
Proportion of subjects defined as High risk by the signature among all subjects
- Global survival [sept 2019-sept 2020]
Time frame between diagnosis date of advanced stage / metastatic stage and date of death or last news
- Progression Free survival [sept 2019-sept 2020]
Time frame between date of diagnosis of advanced stage / metastatic stage and date of either progression or death or last news
Eligibility Criteria
Criteria
Inclusion Criteria:
- Patients with ovarian adenocarcinoma treated in IUCTO Toulouse by primary chemotherapy and for whom diagnosis tumoral sample is available
Exclusion Criteria:
- None
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institut Claudius Regaud Institut Universitaire du cancer Toulouse Oncopole | Toulouse | France | 31059 |
Sponsors and Collaborators
- Institut Claudius Regaud
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 18HLGENF05