Clinical trial NCT02789384: CINSARC Signature and Correlation With Hemotherapy Efficacy in Soft-tissue Sarcomas. A Biomarker Study.
Official title: Prognostic Value of the CINSARC (Complexity Index in Sarcoma) Signature and Correlation With Chemotherapy Efficacy in Soft-tissue Sarcomas. A Biomarker Study. (NEOSarcomics )
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Soft-tissue Sarcomas
Keywords: soft-tissue sarcomas
CINSARC
biomarker
efficacy
pronostic
Lead sponsor: Institut Bergonié
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
name: Ministry of Health, France
First posted: 2016-06-03
Enrollment: 205
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed soft-tissue sarcoma by central review, except if the diagnosis was already confirmed by the RRePS (Réseau de Référence en Pathologie des Sarcomes et des Viscères) Network,
2. Available archived frozen tumor tissue sample or patient consenting to undergo a biopsy of the tumour for research purpose,
3. Non-metastatic disease, for which the use of chemotherapy to "downstage" the sarcoma prior to surgery, is assumed to result in better local tumor control by the multidisciplinary sarcoma team of one of the French reference centers involved in this study,
4. Age ≥ 18 years,
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1,
6. Measurable disease according to RECIST v1.1 outside any previously irradiated field,
7. Neoadjuvant anthracycline-based chemotherapy proposed as the best option by the multidisciplinary sarcoma team of one of the French reference centers involved in this study,
8. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
9. Voluntarily signed and dated written informed consents prior to any study specific procedure,
10. Patients with a social security in compliance with the French Law relating to biomedical research (Article 1121-11 of French Public Health Code).

Exclusion Criteria:

1. Pathological diagnosis different from a soft-tissue sarcoma,
2. Histological subtypes: well-differentiated liposarcoma, alveolar soft-part sarcoma, dermatofibrosarcoma protuberans, clear-cell sarcoma, rhabdomyosarcoma,
3. Previous treatment for the sarcoma,
4. Contra-indication precluding the administration of chemotherapy as assessed by the investigator,
5. Participation to a study involving a medical or therapeutic intervention in the last 30 days,
6. Previous enrolment in the present study,
7. Pregnant or breast feeding women,
8. Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons.

Primary outcomes:
measure: 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.
timeFrame: participants will be followed for the duration of treatment, an expected average of 6-months
Secondary outcomes:
measure: Efficacy of neoadjuvant anthracycline based chemotherapy in terms of proportion of tumour cells identified on the surgical specimen
timeFrame: an expected average of 6 months
measure: Association of the CINSARC signature and histological response based on the proportion of tumour cells identified on the surgical specimen
timeFrame: an expected average of 6 months
measure: Patient's classification by CINSARC signature. Patients will be classified as either low risk CINSARC or high risk
timeFrame: 6 months
measure: Metastasis-free survial is defined following recent guidelines for the definition of survival endpoints in sarcoma trials (Bellera et al. Annals Oncol 2014.
timeFrame: 3 years
measure: 3 -year Overall Survial (OS) defined as the time from study treatment initiation to death (of any cause).
timeFrame: 3 years
measure: Histological response is defined using both 3 histological parameters: proportion of recognizable tumor cells, fibrosis and necrosis in the surgical specimen.
timeFrame: an expected average of 6 months
measure: Identification of molecular mechanisms involved in intrinsic resistance to chemotherapy by correlating the transcriptome data with response to chemotherapy.
timeFrame: an expected average of 6 months
measure: Adverse events related to the biopsy procedure will be graded using the common toxicity criteria from the NCI v4.0.
timeFrame: during 7 days after biopsy
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonié
city: Dijon Cedex
country: France
facility: Centre Georges François Leclerc
city: Lille Cedex
country: France
facility: Centre Oscar Lambret
city: Lyon Cedex 08
country: France
facility: Centre Léon Bérard
city: Marseille Cedex 05
country: France
facility: AP-HM _ Hôpital de la Timone
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest
city: Paris Cedex
country: France
facility: Institut Curie
city: Toulouse Cedex 9
country: France
facility: Institut Claudius Regaud - IUCT-0
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
Study officials:
References: