This is a prospective observational biomarker study including patients with non-metastatic, soft-tissue sarcomas (STS) for whom neoadjuvant chemotherapy is considered as the best option by the multidisciplinary sarcoma team of one of the participating centers.
Even when retrospective statistical identification for a biomarker has been achieved, the ultimate proof of its usefulness in the clinic still requires prospective evidence. Our prospective study aims to validate the prognosis value of the CINSARC signature in a prospective way. Moreover, the neoadjuvant setting is an ideal one to identify molecular predictive factors of sensitivity to chemotherapy by correlating tumor response with genetic profile of STS. Moreover, molecular profiling of treatment-refractory tumor cells may reveal alterations that are associated with drug resistance, metastatic recurrence and disease progression. The identifications of such factors in the neoadjuvant setting may help to improve the management of STS patients in the adjuvant and metastatic settings
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
205
Procedure/Surgery: Newly obtained biopsy if applicable and Blood samples collection. For each patient: * Frozen and paraffin embedded tumor material (archival or new biopsy) will be obtained for genetic profiling * Blood samples will be obtained for genetic profiling and assessment of markers. The classification as CINSARC will be performed for each patient. Patients should be treated by neoadjuvant anthracycline-based chemotherapy. Chemotherapy regimen must contain at least doxorubicin (dose range: 60 -75 mg/m²) and ifosfamide (dose range: 2.5-3g/m²) to be delivered on a 21-days cycle basis up to 6 cycles prior surgery. After neoadjuvant chemotherapy completion, patients will be treated by surgery followed or not by radiotherapy. All patients should be managed according to the usual medical practices.
Institut Bergonié
Bordeaux, France
RECRUITINGCentre Georges François Leclerc
Dijon, France
RECRUITINGCentre Oscar Lambret
Lille, France
Assessment of antitumor activity of neoadjuvant anthracycline based chemotherapy. Efficacy will be defined based on complete response, partial response and stable disease observed during treatment following RECIST v1.1 criteria.
Time frame: participants will be followed for the duration of treatment, an expected average of 6-months
Efficacy of neoadjuvant anthracycline based chemotherapy in terms of proportion of tumour cells identified on the surgical specimen
Time frame: an expected average of 6 months
Association of the CINSARC signature and histological response based on the proportion of tumour cells identified on the surgical specimen
Time frame: an expected average of 6 months
Patient's classification by CINSARC signature. Patients will be classified as either low risk CINSARC or high risk
Time frame: 6 months
Metastasis-free survial is defined following recent guidelines for the definition of survival endpoints in sarcoma trials (Bellera et al. Annals Oncol 2014.
Time frame: 3 years
3 -year Overall Survial (OS) defined as the time from study treatment initiation to death (of any cause).
Time frame: 3 years
Histological response is defined using both 3 histological parameters: proportion of recognizable tumor cells, fibrosis and necrosis in the surgical specimen.
Time frame: an expected average of 6 months
Identification of molecular mechanisms involved in intrinsic resistance to chemotherapy by correlating the transcriptome data with response to chemotherapy.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Centre Léon Bérard
Lyon, France
RECRUITINGInstitut Paoli Calmettes
Marseille, France
RECRUITINGAP-HM _ Hôpital de la Timone
Marseille, France
RECRUITINGInstitut de Cancérologie de l'Ouest
Nantes, France
RECRUITINGInstitut Curie
Paris, France
NOT_YET_RECRUITINGInstitut Claudius Regaud - IUCT-0
Toulouse, France
RECRUITINGInstitut Gustave Roussy
Villejuif, France
NOT_YET_RECRUITINGTime frame: an expected average of 6 months
Adverse events related to the biopsy procedure will be graded using the common toxicity criteria from the NCI v4.0.
Time frame: during 7 days after biopsy