Benefit of Intensified Peri-operative Chemotherapy Within High-risk CINSARC Patients With Resectable Soft-tissue Sarcomas

Phase 3

Recruiting

• Conditions: Non-metastatic Soft-tissue Sarcoma; Resectable
• Interventions: Drug: At the discretion of the investigator; Drug: Doxorubicin; Drug: Ifosfamide or dacarbazine

• Registration Number: NCT03805022
• Lead Sponsor: Institut Bergonié

Brief Summary

The primary objective of this trial is to investigate whether the addition of 3 additional neo-adjuvant cycles of chemotherapy (doxorubicin based chemotherapy) to standard management according to the ISG-STS 10-01 study (3 cycles of neoadjuvant doxorubicin based chemotherapy + surgery +/- radiotherapy) improves the outcome of high-risk CINSARC patients with resectable soft-tissue sarcoma (STS). Primary endpoint is metastatic progression-free survival (M-PFS, after 3 years of follow-up).

Detailed Description

For high-risk CINSARC patients, this is a multicenter randomized two-arm phase III trial, with a ratio 1:1:

* Arm A: standard management (3 cycles of neoadjuvant doxorubicin based chemotherapy + surgery +/- radiotherapy)

* Arm B: experimental arm (6 cycles of neoadjuvant doxorubicin based chemotherapy + surgery +/- radiotherapy)

For low-risk CINSARC patients, this a multicenter prospective cohort with treatment at the discretion of the investigator.

Study Timeline

• Study First Submitted: 2019-01-10
• Study First Submitted QC: 2019-01-14
• Study First Posted: 2019-01-15
• Study Start: 2019-02-14
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-28
• Last Update Posted: 2023-03-01
• Primary Completion: 2025-02
• Study Completion: 2025-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 351

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	Ifosfamide or dacarbazine	Experimental-Arm phase III high-risk CINSARC: Patients will be treated by doxorubicin (60 or 75mg/m² day or 20 or 25 mg/m² per day from day1 to day 3) + ifosfamide (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices of a 21-days cycle for up to 6 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).
Arm A	Ifosfamide or dacarbazine	Control-Arm phase III high-risk CINSARC: Patients will be treated by doxorubicin (60 or 75mg/m² day or 20- or 25 mg/m² per day from day1 to day 3) + ifosfamide (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices of a 21-days cycle for up to 3 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).
Prospective cohort	At the discretion of the investigator	Patients will be treated at the discretion of the investigator
Arm A	Doxorubicin	Control-Arm phase III high-risk CINSARC: Patients will be treated by doxorubicin (60 or 75mg/m² day or 20- or 25 mg/m² per day from day1 to day 3) + ifosfamide (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices of a 21-days cycle for up to 3 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).
Arm B	Doxorubicin	Experimental-Arm phase III high-risk CINSARC: Patients will be treated by doxorubicin (60 or 75mg/m² day or 20 or 25 mg/m² per day from day1 to day 3) + ifosfamide (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices of a 21-days cycle for up to 6 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).

Primary Outcome Measures

Name	Time	Method
Metastasis progression-free survival in High-risk CINSARC patients	3 years	Metastasis progression-free survival (M-PFS) defined as the time interval between the date of randomization and the date of death or distant progression.

Secondary Outcome Measures

Name	Time	Method
Loco-regional relapse-free survival in High-risk CINSARC patients	3 years	Loco-regional relapse-free survival (LR-RFS) defined as the time interval between the randomization date and the date of death or loco-regional progression.
Progression-free survival in High-risk CINSARC patients	3 years	Progression-free survival (PFS) defined as the time interval between the randomization date and the date of death or progression (as per RECIST v1.1).
Overall survival in High-risk CINSARC patients	3 years	Overall survival (OS) defined as the time interval between the randomization date and the date of death.
Best overall response in High-risk CINSARC patients	Throughout the treatment period, an average of 6 months	Best overall response under treatment as per RECIST v1.1.
Histological response in High-risk CINSARC patients	An average of 6 months	Histological response defined as the proportion of recognizable cells on the tumor sample.
Safety profile in High-risk CINSARC patients	Throughout the treatment period, an average of 6 months	Toxicity graded using the common toxicity criteria from the NCI v5.
Progression-free survival in Low-risk CINSARC patients	3 years	Progression-free survival defined as the time interval between the randomization date and the date of death or progression (as per RECIST v1.1).
Metastasis progression-free survival in Low-risk CINSARC patients	3 years	Metastasis progression-free survival defined as the time interval between the inclusion date and the date of death or distant progression.
Loco-regional progression-free survival in Low-risk CINSARC patients	3 years	Description of the treatment efficacy in terms of 3-years loco-regional progression-free survival defined as the time interval between the randomization date and the date of death or loco-regional progression.
Overall survival in Low-risk CINSARC patients	3 years	Overall survival defined as the time interval between the inclusion date and the date of death.

Trial Locations

Locations (10)

CHU Dupuytren; 🇫🇷 Limoges, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

Centre Georges François Leclerc; 🇫🇷 Dijon, France

Institut Bergonie; 🇫🇷 Bordeaux, France

Insitut du Cancer; 🇫🇷 Montpellier, France

Centre Léon Bérard; 🇫🇷 Lyon Cedex 08, France

Institut Paoli Calmettes; 🇫🇷 Marseille, France

Institut de Cancérologie de l'Ouest - Site René Gauducheau; 🇫🇷 Saint-Herblain, France

CHRU Strasbourg; 🇫🇷 Strasbourg, France

Institut Claudius Regaud; 🇫🇷 Toulouse, France