CINSARC Genomic Signature as Predictor of Resectability of Ovarian Adenocarcinoma (OVASARC)

The CINSARC Genomic Signature as a Predictor of Resectability of High Grade Serous Ovarian Adenocarcinomas

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Adenocarcinoma
• Intervention / Treatment: Other: CINSARC signature

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 Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31059
    • Institut Claudius Regaud Institut Universitaire du cancer Toulouse Oncopole

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Retrospective study on medical, clinical, pathologic data from patients primary treated for ovarian adenocarcinoma . 150 cases analyzed

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The main endpoint is the sensitivity of the CINSARC signature to identify surgical resectability after neoadjuvant chemotherapy.	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	sept 2019-sept 2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specificity of the CINSARC signature	Proportion of subjects defined as high risk by the signature and having not been resected among patients having not been resected	sept 2019-sept 2020
Positive predictive value of the signature	Proportion of subjects defined as Low risk by the signature among all subjects	sept 2019-sept 2020
Negative predictive value of the signature	Proportion of subjects defined as High risk by the signature among all subjects	sept 2019-sept 2020
Global survival	Time frame between diagnosis date of advanced stage / metastatic stage and date of death or last news	sept 2019-sept 2020
Progression Free survival	Time frame between date of diagnosis of advanced stage / metastatic stage and date of either progression or death or last news	sept 2019-sept 2020

Collaborators and Investigators

• Sponsor: Institut Claudius Regaud

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2019
• Primary Completion (Actual): September 15, 2020
• Study Completion (Actual): December 23, 2021

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): January 30, 2020

Study Record Updates

• Last Update Posted (Actual): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 22, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Adenocarcinoma; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: 18HLGENF05

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No