Intensified pre-surgery chemotherapy for adults with high-risk resectable soft-tissue sarcoma

Phase III Trial Investigating the Potential Benefit of Intensified Peri-operative Chemotherapy With in High-risk CINSARC Patients With Resectable Soft-tissue SARComas

This study will try giving three extra cycles of doxorubicin-based chemotherapy before surgery to adults with resectable, high‑risk CINSARC soft-tissue sarcoma to see if it lowers the chance of the cancer spreading.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 351 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institut Bergonié (other)
• Drugs / interventions: chemotherapy, doxorubicin
• Locations: 10 sites (Bordeaux and 9 other locations)
• Trial ID: NCT03805022 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized phase III trial comparing standard neoadjuvant doxorubicin‑based chemotherapy (three cycles) versus an intensified regimen (six cycles) given before surgery, with radiotherapy added when appropriate. High‑risk patients by the CINSARC signature are randomized 1:1 to the two arms; low‑risk patients are followed in a prospective cohort managed at investigator discretion. Chemotherapy may include doxorubicin with ifosfamide or dacarbazine per investigator choice. The primary endpoint is metastatic progression‑free survival measured over three years of follow‑up.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed, non‑metastatic, resectable soft‑tissue sarcoma that is FNCLCC grade 2–3, classified as high‑risk by CINSARC, with ECOG performance status 0–1, measurable disease, no prior treatment, and an available archived tumor sample.

Not a fit: Patients with low‑risk CINSARC tumors, metastatic or unresectable disease, poor performance status, or prior treatment for the disease are unlikely to benefit from the intensified neoadjuvant approach being tested here.

Why it matters

Potential benefit: If successful, intensified preoperative chemotherapy could reduce metastatic recurrences and improve metastasis‑free survival and overall outcomes for high‑risk patients.

How similar studies have performed: Neoadjuvant doxorubicin‑based regimens (such as the ISG‑STS 10‑01 backbone) have shown activity in sarcoma, but using three additional preoperative cycles specifically in high‑risk CINSARC patients is a newer approach without definitive proof of benefit.

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.

Where this trial is running

Bordeaux and 9 other locations

• Institut Bergonie — Bordeaux, France (RECRUITING)
• Centre Georges François Leclerc — Dijon, France (RECRUITING)
• CHU Dupuytren — Limoges, France (RECRUITING)
• Centre Léon Bérard — Lyon, France (RECRUITING)
• Institut Paoli Calmettes — Marseille, France (RECRUITING)
• Insitut du Cancer — Montpellier, France (RECRUITING)
• Institut de Cancérologie de l'Ouest - Site René Gauducheau — Saint-Herblain, France (RECRUITING)
• CHRU Strasbourg — Strasbourg, France (RECRUITING)
• Institut Claudius Regaud — Toulouse, France (RECRUITING)
• Institut Gustave Roussy — Villejuif, France (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Antoine ITALIANO, MD, PhD

Conditions: Non-metastatic Soft-tissue Sarcoma, Resectable, Solid tumor, Phase III trial, Soft-tissue sarcoma, Non-metastatic