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

NCT ID: NCT03805022

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 351 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-14
• Study Completion Date: 2028-12-31

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.

Conditions

Non-metastatic Soft-tissue Sarcoma; Resectable

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

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).

Group Type: EXPERIMENTAL

Doxorubicin

Intervention Type: DRUG

A treatment cycle consists of 3 weeks. Doxorubicin will be administered from day 1 to day 3 (60 or 75mg/m² day or 20 or 25 mg/m² per day), repeated every 3 weeks, up to 3 cycles.

Ifosfamide or dacarbazine

Intervention Type: DRUG

A treatment cycle consists of 3 weeks. Treatment may continue up to 3 cycles. Ifosfamide will be administered from day 1 to day 3 (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, repeated every 3 weeks, up to 3 cycles.

Arm B

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).

Group Type: EXPERIMENTAL

Doxorubicin

Intervention Type: DRUG

A treatment cycle consists of 3 weeks. Doxorubicin will be administered from day 1 to day 3 (60 or 75mg/m² day or 20 or 25 mg/m² per day), repeated every 3 weeks, up to 6 cycles.

Ifosfamide or dacarbazine

Intervention Type: DRUG

A treatment cycle consists of 3 weeks. Ifosfamide will be administered from day 1 to day 3 (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, repeated every 3 weeks, up to 6 cycles.

Prospective cohort

Patients will be treated at the discretion of the investigator

Group Type: EXPERIMENTAL

At the discretion of the investigator

Intervention Type: DRUG

Drug at the discretion of the investigator.

Interventions

Doxorubicin

A treatment cycle consists of 3 weeks. Doxorubicin will be administered from day 1 to day 3 (60 or 75mg/m² day or 20 or 25 mg/m² per day), repeated every 3 weeks, up to 3 cycles.

Intervention Type: DRUG

Ifosfamide or dacarbazine

A treatment cycle consists of 3 weeks. Treatment may continue up to 3 cycles. Ifosfamide will be administered from day 1 to day 3 (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, repeated every 3 weeks, up to 3 cycles.

Intervention Type: DRUG

Doxorubicin

A treatment cycle consists of 3 weeks. Doxorubicin will be administered from day 1 to day 3 (60 or 75mg/m² day or 20 or 25 mg/m² per day), repeated every 3 weeks, up to 6 cycles.

Intervention Type: DRUG

Ifosfamide or dacarbazine

A treatment cycle consists of 3 weeks. Ifosfamide will be administered from day 1 to day 3 (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, repeated every 3 weeks, up to 6 cycles.

Intervention Type: DRUG

At the discretion of the investigator

Drug at the discretion of the investigator.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed soft-tissue sarcoma by the RRePS (Réseau de Référence en Pathologie des Sarcomes et des Viscères) network, as recommended by the French NCI,

2. Grade 2 or 3 according to the FNCLCC grading system,

3. Available archived tumour sample for research purpose,

4. Non-metastatic and resectable disease,

5. No prior treatment for the disease under study,

6. Age ≥ 18 years,

7. Life expectancy ≥ 3 months,

8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1,

9. Patients must have measurable disease (lesion in previously irradiated field can be considered as measurable if progressive at inclusion according to RECIST 1.1) defined as per RECIST v1.1 with at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm or ≥ 15mm in case of adenopathy,

10. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for one year after discontinuation of treatment. Acceptable methods of contraception include intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier. Subjects of childbearing potential are those who have not been surgically sterilized (e.g., vasectomy for males and hysterectomy for females) or have not been free from menses for ≥ 1 year,

11. Voluntarily signed and dated written informed consents prior to any study specific procedure,

12. Patients with a social security in compliance with the French law.

Exclusion Criteria

1. Soft-tissue sarcoma with the following histological subtypes: well-differentiated liposarcoma, alveolar soft-part sarcoma, dermatofibrosarcoma protuberans, clearcell sarcoma, embryonal and alveolar rhabdomyosarcoma,

2. 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,

3. Any other contraindication to anthracycline, ifosfamide or dacarbazine chemotherapy,

4. Participation to a study involving a medical or therapeutic intervention in the last 28 days,

5. Known infection with HIV, hepatitis B, or hepatitis C,

6. Females who are pregnant or breast-feeding,

7. Other medical conditions may interfere with the conduct of the study and, in the judgment of the investigator, would make the patient inappropriate for entry into this study,

8. Individuals deprived of liberty or placed under legal guardianship,

9. Unwillingness or inability to comply with the study protocol for any reason.

Additional criteria for randomization :

1. High-risk CINSARC signature,

2. No more than two cycle of neo-adjuvant anthracycline-based chemotherapy before randomization.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Chugai Pharma France

INDUSTRY

Sponsor Role: collaborator

Institut Bergonié

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institut Bergonie

Bordeaux, , France

Site Status: RECRUITING

Centre Georges François Leclerc

Dijon, , France

Site Status: RECRUITING

CHU Dupuytren

Limoges, , France

Site Status: RECRUITING

Centre Léon Bérard

Lyon, , France

Site Status: RECRUITING

Institut Paoli Calmettes

Marseille, , France

Site Status: RECRUITING

Insitut du Cancer

Montpellier, , France

Site Status: RECRUITING

Institut de Cancérologie de l'Ouest - Site René Gauducheau

Saint-Herblain, , France

Site Status: RECRUITING

CHRU Strasbourg

Strasbourg, , France

Site Status: RECRUITING

Institut Claudius Regaud

Toulouse, , France

Site Status: RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status: NOT_YET_RECRUITING

Countries

France

Central Contacts

Antoine ITALIANO, MD, PhD

Role: CONTACT

a.italiano@bordeaux.unicancer.fr

+33 5.56.33.33.33

Simone MATHOULIN-PELISSIER, MD, PhD

Role: CONTACT

m.mathoulin@bordeaux.unicancer.fr

Facility Contacts

Antoine ITALIANO, MD, PhD

Role: primary

a.italiano@bordeaux.unicancer.fr

Nicolas ISAMBERT

Role: primary

Valérie LEBRUN-LY, MD

Role: primary

Jean-Yves BLAY, MD, PhD

Role: primary

François BERTUCCI, MD, PhD

Role: primary

Nelly FIRMIN, MD

Role: primary

nelly.firmin@icm.unicancer.fr

Emmanuelle BOMPAS, MD

Role: primary

Jean-Emmanuel KURTZ, MD, PhD

Role: primary

je.kurtz@icans.eu

Christine CHEVREAU

Role: primary

chevreau.christine@iuct-oncopole.fr

Axel LE CESNE, MD

Role: primary

Other Identifiers

2018-000186-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IB 2017-04

Identifier Type: -

Identifier Source: org_study_id