Interest of peri operative CHemotherapy In patients with CINSARC high-risk localized grade 1 or 2 Soft Tissue Sarcoma.
- Conditions
- Soft Tissue SarcomaMedDRA version: 20.0Level: PTClassification code 10075333Term: Soft tissue sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003014-13-FR
- Lead Sponsor
- INSTITUT CLAUDIUS REGAUD
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
1.Diagnosis of soft-tissue sarcoma, histologically confirmed by RRePS (Réseau de Référence en Pathologie des Sarcomes et des Viscères) network
2.According to FNCLCC grading system, grade 2 and grade 1 tumors
3.Resectable and localized disease after appropriate extension work-up (including at least a chest-CT)
4.Available archived FFPE tumor sample in sufficient quantity to allow CINSARC qualification
5.Age = 18 years
6.Eastern Cooperative Oncology Group (ECOG) performance status = 2
7.Life expectancy of at least 12 weeks after the start of the treatment
8.Acceptable hematologic function (within 72 hours of eligibility assessment): Absolute neutrophil count (ANC) = 1.5 G/L, Platelet count = 100 G/L and Hemoglobin > 9g/dL
9.Acceptable renal function within 72 hours of eligibility assessment: Serum creatinine = 1.5 x ULN or calculated creatinine clearance = 60 mL/min (by the Cockcroft and Gault formula)
10.Acceptable liver function: Bilirubin = 1.5 x upper limit of normal (ULN), AST (SGOT) and ALT (SGPT) = 2.5 x ULN
11.Normal LVEF (>50%) measured by echocardiography or isotopic ventriculography
12.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.
13.Signed written informed consent
14.Patient affiliated to a Social Health Insurance in France.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1.Soft-tissue sarcoma with the following histological subtypes: well-differentiated liposarcomas, alveolar soft-part sarcoma, dermatofibrosarcoma protuberans, clear-cell sarcoma, epithelioid sarcoma, alveolar or embryonal rhabdomyosarcoma
2.Primitive cutaneous, retroperitoneal, uterus or visceral STS
3.Metastatic disease
4.Previous or ongoing treatment for the sarcoma (with the exception of a surgery for diagnosis intend)
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
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.
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 FNCLCC grade 1/2 STS, considered as high-risk according to CINSARC.;Secondary Objective: The secondary objectives are:<br>-To compare the two therapeutics strategies in high-risk CINSARC patients with grade 1/2 resectable soft-tissue sarcoma (STS), in terms of:<br>oDisease-free survival,<br>oOverall survival,<br>oSafety profile.<br>-To prospectively validate the prognostic value of CINSARC signature in grade 1/2 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.;Timepoint(s) of evaluation of this end point: Five years post-randomisation
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary endpoints are:<br>•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.<br>•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.<br>•Safety will be assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v5.0).;Timepoint(s) of evaluation of this end point: Five years post-randomisation faor each endpoint