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

Institut Claudius Regaud28 sites in 1 country600 target enrollmentOctober 9, 2020

ConditionsSoft Tissue Sarcoma

InterventionsStandard of care Standard of care + chemotherapy

Overview

Phase: Phase 3
Intervention: Standard of care
Conditions: Soft Tissue Sarcoma
Sponsor: Institut Claudius Regaud
Enrollment: 600
Locations: 28
Primary Endpoint: Metastasis-free survival defined by the delay between randomization and the appearance of metastatic.
Status: Recruiting
Last Updated: 18 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

October 9, 2020

End Date

October 1, 2032

Last Updated

18 days ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Institut Claudius Regaud

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Diagnosis of soft-tissue sarcoma, histologically confirmed by RRePS (Réseau de Référence en Pathologie des Sarcomes et des Viscères) network
•According to FNCLCC grading system, grade 1, 2 or 3 tumors
•Resectable and localized disease after appropriate extension work-up (including at least a chest-CT)
•6 weeks or less between surgical excision and inclusion (if performed before inclusion)
•Available archived FFPE tumor sample in sufficient quantity to allow CINSARC qualification
•Age ≥ 18 years
•Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
•Life expectancy of at least 12 weeks after the start of the treatment
•Women should be post-menopaused or willing to accept the use of an effective contraceptive regimen during the treatment period and at least 12 months (ifosfamide treatment) or 6 months (dacarbazine treatment) after the end of the treatment period. All non-menopaused women should have a negative pregnancy test within 72 hours prior to registration. Men should accept to use an effective contraception during treatment period and at least 3 months after the end of the study treatment.
•Signed written informed consent

Exclusion Criteria

•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
•Primitive cutaneous, retroperitoneal, uterus or visceral STS
•Metastatic disease
•Previous or ongoing treatment for the sarcoma (with the exception of surgical excision)
•Contra-indication for Doxorubicin, Ifosfamide and Dacarbazine treatments
•Prior therapy with ifosfamide or cyclophosphamide or other nitrogen mustards, and prior therapy with anthracyclines
•Prior mediastinal/cardiac radiotherapy
•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
•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
•Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy

Arms & Interventions

Control arm

Intervention: Standard of care

Experimental arm

Intervention: Standard of care + chemotherapy

Outcomes

Primary Outcomes

Metastasis-free survival defined by the delay between randomization and the appearance of metastatic.

Time Frame: 5 years for each patient

Secondary Outcomes

Safety assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v5.0).(4 months for each patient)
Disease-free survival defined by the delay between randomization and first relapse (local, regional, or distant) or death from any cause.(5 years for each patient)
Overall survival defined by the delay between randomization and death from any cause.(5 years for each patient)