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

NCT03805022 | Recruiting Phase 3 DMC

• 2 other identifiers: IB 2017-042018-000186-36
• Study Type: interventional
• Target: 351
• Locations: 1 country
• Sites: 10

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).

Conditions

Non-metastatic Soft-tissue Sarcoma; Resectable

Keywords

Solid tumor; Phase III trial; Soft-tissue sarcoma; Resectable; Non-metastatic

Outcome Measures

Primary Outcomes (1)

• Metastasis progression-free survival in High-risk CINSARC patients

  Metastasis progression-free survival (M-PFS) defined as the time interval between the date of randomization and the date of death or distant progression.

  3 years

Secondary Outcomes (10)

• Loco-regional relapse-free survival in High-risk CINSARC patients

  3 years

• Progression-free survival in High-risk CINSARC patients

  3 years

• Overall survival in High-risk CINSARC patients

  3 years

• Best overall response in High-risk CINSARC patients

  Throughout the treatment period, an average of 6 months

• Histological response in High-risk CINSARC patients

  An average of 6 months

Study Arms (3)

Arm A

EXPERIMENTAL

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).

Drug: Doxorubicin; Drug: Ifosfamide or dacarbazine

Arm B

EXPERIMENTAL

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).

Drug: Doxorubicin; Drug: Ifosfamide or dacarbazine

Prospective cohort

EXPERIMENTAL

Patients will be treated at the discretion of the investigator

Drug: At the discretion of the investigator

Interventions

Doxorubicin 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.

Arm A

Ifosfamide or dacarbazine 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 A

At the discretion of the investigator DRUG

Drug at the discretion of the investigator.

Prospective cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• Grade 2 or 3 according to the FNCLCC grading system,
• Available archived tumour sample for research purpose,
• Non-metastatic and resectable disease,
• No prior treatment for the disease under study,
• Age ≥ 18 years,
• Life expectancy ≥ 3 months,
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1,
• 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,
• Voluntarily signed and dated written informed consents prior to any study specific procedure,
• Patients with a social security in compliance with the French law.

You may not qualify if:

• Soft-tissue sarcoma with the following histological subtypes: well-differentiated liposarcoma, alveolar soft-part sarcoma, dermatofibrosarcoma protuberans, clearcell sarcoma, embryonal and alveolar rhabdomyosarcoma,
• 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,
• Any other contraindication to anthracycline, ifosfamide or dacarbazine chemotherapy,
• Participation to a study involving a medical or therapeutic intervention in the last 28 days,
• Known infection with HIV, hepatitis B, or hepatitis C,
• Females who are pregnant or breast-feeding,
• 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,
• Individuals deprived of liberty or placed under legal guardianship,
• Unwillingness or inability to comply with the study protocol for any reason.
• Additional criteria for randomization :
• High-risk CINSARC signature,
• No more than two cycle of neo-adjuvant anthracycline-based chemotherapy before randomization.

Sponsors & Collaborators

• Institut Bergonié: lead
• Novartis: collaborator
• Chugai Pharma France: collaborator

Study Sites (10)

Institut Bergonie

Bordeaux, 33076, France

RECRUITING

Centre Georges François Leclerc

Dijon, 21079, France

RECRUITING

CHU Dupuytren

Limoges, 87042, France

RECRUITING

Centre Léon Bérard

Lyon, 69373, France

RECRUITING

Institut Paoli Calmettes

Marseille, 13273, France

RECRUITING

Insitut du Cancer

Montpellier, 34298, France

RECRUITING

Institut de Cancérologie de l'Ouest - Site René Gauducheau

Saint-Herblain, 44805, France

RECRUITING

CHRU Strasbourg

Strasbourg, 67200, France

RECRUITING

Institut Claudius Regaud

Toulouse, 31052, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94800, France

NOT YET RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

Doxorubicin; Ifosfamide; Dacarbazine

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazenes; Imidazoles; Azoles

Central Study Contacts

Antoine ITALIANO, MD, PhD

CONTACT

+33 5.56.33.33.33; a.italiano@bordeaux.unicancer.fr

Simone MATHOULIN-PELISSIER, MD, PhD

CONTACT

m.mathoulin@bordeaux.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter trial with: * An open randomized two-arm phase III trial for high-risk CINSARC patients assessing whether the addition of 3 additional neo-adjuvant cycles of chemotherapy (doxorubicin based chemotherapy) to standard management (3 cycles of neoadjuvant anthracycline based chemotherapy + surgery +/- radiotherapy) improves the outcome of patients * a prospective cohort for low-risk CINSARC patients.

Study Record Dates

• First Submitted: January 10, 2019
• First Posted: January 15, 2019
• Study Start: February 14, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: October 2, 2025

Record last verified: 2025-10

Locations

FR (10)