Interest of peri operative CHemotherapy In patients with CINSARC highrisk localized Soft Tissue Sarcoma.

Phase 1

Recruiting

• Conditions: Soft Tissue Sarcoma; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2024-515384-62-00
• Lead Sponsor: Oncopole Claudius Regaud

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-06-13
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1.Diagnosis of soft-tissue sarcoma, histologically confirmed by RRePS (Réseau de Référence en Pathologie des Sarcomes et des Viscères) network, 10.Signed written informed consent, 11.Patient affiliated to a Social Health Insurance in France, 1.High-risk CINSARC signature (FOR THE RANDOMIZED PHASE III STUDY), 2.Acceptable hematologic function (within 72 hours prior randomization): Absolute neutrophil count (ANC) = 1.5 G/L, Platelet count = 100 G/L and Hemoglobin > 9g/dL, 3.Acceptable renal function within 72 hours prior randomization: Serum creatinine = 1.5 x ULN or calculated creatinine clearance = 60 mL/min (by the Cockcroft and Gault formula), 4.Acceptable liver function: Bilirubin = 1.5 x upper limit of normal (ULN), AST (SGOT) and ALT (SGPT) = 2.5 x ULN, 5.Normal LVEF (>50%) measured by echocardiography or isotopic ventriculography, 2.According to FNCLCC grading system, grade 1, 2 or 3 tumors, 2.According to FNCLCC grading system, grade 1, 2 or 3 tumors 3.Resectable and localized disease after appropriate extension work-up (including at least a chest-CT), 4.6 weeks or less between surgical excision and inclusion (if performed before inclusion), 5.Available archived FFPE tumor sample in sufficient quantity to allow CINSARC qualification, 6.Age = 18 years, 7.Eastern Cooperative Oncology Group (ECOG) performance status = 2, 8.Life expectancy of at least 12 weeks after the start of the treatment, 9.Women should be post-menopaused or willing to accept the use an effective contraceptive regimen during the treatment period and at least 12 months after the end of the treatment period. All non-menopaused women should have a negative pregnancy test within 72 hours prior to registration

Exclusion Criteria

1.Soft-tissue sarcoma with the following histological subtypes: welldifferentiated liposarcomas, alveolar soft-part sarcoma, dermatofibrosarcoma protuberans, clear-cell sarcoma, epithelioid sarcoma, alveolar or embryonal rhabdomyosarcoma, 10.Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy, 11.Known infection with HIV, hepatitis B, or hepatitis C, 12.Women who are breastfeeding, pregnant or who plan to become pregnant while in the trial, 13.Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study, 14.Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice), 15.Patient unable to comply with the protocol for any reason, 2.Primitive cutaneous, retroperitoneal, uterus or visceral STS, 3.Metastatic disease, 4.Previous or ongoing treatment for the sarcoma (with the exception of surgical excision), 5.Contra-indication for Doxorubicin, Ifosfamide and Dacarbazine treatments, 6.Prior therapy with ifosfamide or cyclophosphamide or other nitrogen mustards, and prior therapy with anthracyclines, 7.Prior mediastinal/cardiac radiotherapy, 8.History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia, myocardial infarction within 6 months prior to study entry, 9.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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is 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.;Secondary Objective: To compare the two therapeutics strategies in high-risk CINSARC patients with resectable soft-tissue sarcoma (STS), in terms of: Disease-free survival, Overall survival, Safety profile., To prospectively validate the prognostic value of CINSARC signature in STS treated by standard treatment.;Primary end point(s): The primary endpoint is Metastasis-free survival (MFS). MFS is defined by the delay between randomization and the appearance of metastatic disease or death from any cause.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Disease-free survival (DFS) is defined by the delay between randomization and first relapse (local, regional, or distant) or death from any cause. Patients still alive at the time of analysis (including lost to follow-up) without appearance of relapse will be censored at the last disease assessment date.;Secondary end point(s):Overall survival (OS) is defined by the delay between randomization and death from any cause. Patients still alive at the time of analysis (including lost to follow-up) will be censored at the last known alive date.;Secondary end point(s):Safety will be assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v5.0).