Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Carcinoma

Carcinoma, Ovarian Epithelial

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

CINSARC signature

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.

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

CINSARC Genomic Signature as Predictor of Resectability of Ovarian Adenocarcinoma

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

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

Proportion of subjects defined as high risk by the signature and having not been resected among patients having not been resected

Proportion of subjects defined as Low risk by the signature among all subjects

Proportion of subjects defined as High risk by the signature among all subjects

Time frame between diagnosis date of advanced stage / metastatic stage and date of death or last news

Time frame between date of diagnosis of advanced stage / metastatic stage and date of either progression or death or last news

Institut Claudius Regaud

Sarcoma

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Doxorubicin

Liposomal doxorubicin

Ifosfamide

Dacarbazine

Isophosphamide mustard

Doxorubicine with Ifosfamide during 4 cycles Q3W Or Doxorubicine with Dacarbazine during 4 cycles Q3W (for patients with Leiomyosarcoma)

Standard of care + chemotherapy

Surgical excision with external radiotherapy (if applicable)

Standard of care

Thibaud VALENTIN

Loïc CHAIGNEAU

Antoine ITALIANO

Zoé NEVIERE

Pascale DUBRAY-LONGERAS

Alice HERVIEU

Mathieu LARAMAS

Valérie LE BRUN-LY

Armelle DUFRESNE

François BERTUCCI

Florence DUFFAUD

Nelly FIRMIN

Esma SAADA-BOUZID

Pascaline BOUDOU-ROUQUETTE

Nicolas ISAMBERT

Pauline SOIBINET-OUDOT

Angélique BRUNOT

Cécile GUILLEMET

Emmanuelle BOMPAS

Justine GANTZER

Maria RIOS

Phase III, multicenter, randomized open-label and comparative study designed to demonstrate whether adding 4 cycles of peri-operative doxorubicin-based chemotherapy improves metastasis-free survival as compared with standard management in patients with resectable STS, considered as high-risk according to CINSARC (Complexity Index in SARComas) signature.

After signed informed consent, patients considered as eligible to CHIC-STS study by the investigator will be enrolled in the study and a molecular screening will be performed (600 patients will be screened).

Patients considered as low-risk according to CINSARC signature will be treated at the discretion of the clinicians (prospective cohort).

Patients considered as high-risk according to CINSARC signature will be randomized in the open-label multicenter phase III trial and assigned in one of the two following treatments arms:

* Arm A (control arm): Standard of care (surgical excision +/- external radiotherapy).
* Arm B (experimental arm): Standard of care + 4 cycles of intravenous chemotherapy during 12 weeks.

A total of 250 patients will have to be randomized with 125 patients in each arm.

Interest of Peri Operative CHemotherapy In Patients With CINSARC High-risk Localized Soft Tissue Sarcoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
CINSARC Genomic Signature as Predictor of Resectability of Ovarian Adenocarcinoma	NCT04248231	Ovarian Adenoca...	CINSARC signatu...	18 Years -	Institut Claudius Regaud
Interest of Peri Operative CHemotherapy In Patients With CINSARC High-risk Localized Soft Tissue Sarcoma	NCT04307277	Soft Tissue Sar...	Standard of car... Standard of car...	18 Years -	Institut Claudius Regaud

Spots Global Cancer Trial Database for cinsarc signature