CINSARC Genomic Signature as Predictor of Resectability of Ovarian Adenocarcinoma

Completed

• Conditions: Ovarian Adenocarcinoma

• Registration Number: NCT04248231
• Lead Sponsor: Institut Claudius Regaud

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 :

* to better select patients accessible to full interval surgery

* 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.

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 Timeline

• Study Start: 2019-09-15
• Study First Submitted: 2020-01-27
• Study First Submitted QC: 2020-01-29
• Study First Posted: 2020-01-30
• Primary Completion: 2020-09-15
• Study Completion: 2021-12-23
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-22
• Last Update Posted: 2022-12-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• Patients with ovarian adenocarcinoma treated in IUCTO Toulouse by primary chemotherapy and for whom diagnosis tumoral sample is available

Exclusion Criteria

• None

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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

Trial Locations

Locations (1)

Institut Claudius Regaud Institut Universitaire du cancer Toulouse Oncopole; 🇫🇷 Toulouse, France