Clinical trial NCT03805022: Benefit of Intensified Peri-operative Chemotherapy Within High-risk CINSARC Patients With Resectable Soft-tissue Sarcomas
Official title: Phase III Trial Investigating the Potential Benefit of Intensified Peri-operative Chemotherapy With in High-risk CINSARC Patients With Resectable Soft-tissue SARComas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Non-metastatic Soft-tissue Sarcoma
Resectable
Keywords: Solid tumor
Phase III trial
Soft-tissue sarcoma
Resectable
Non-metastatic
Lead sponsor: Institut Bergonié
Sponsor class: OTHER
Collaborators: name: Novartis
name: Chugai Pharma France
First posted: 2019-01-15
Enrollment: 351
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Metastasis progression-free survival in High-risk CINSARC patients
timeFrame: 3 years
Secondary outcomes:
measure: Loco-regional relapse-free survival in High-risk CINSARC patients
timeFrame: 3 years
measure: Progression-free survival in High-risk CINSARC patients
timeFrame: 3 years
measure: Overall survival in High-risk CINSARC patients
timeFrame: 3 years
measure: Best overall response in High-risk CINSARC patients
timeFrame: Throughout the treatment period, an average of 6 months
measure: Histological response in High-risk CINSARC patients
timeFrame: An average of 6 months
measure: Safety profile in High-risk CINSARC patients
timeFrame: Throughout the treatment period, an average of 6 months
measure: Progression-free survival in Low-risk CINSARC patients
timeFrame: 3 years
measure: Metastasis progression-free survival in Low-risk CINSARC patients
timeFrame: 3 years
measure: Loco-regional progression-free survival in Low-risk CINSARC patients
timeFrame: 3 years
measure: Overall survival in Low-risk CINSARC patients
timeFrame: 3 years
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonie
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Limoges
country: France
facility: CHU Dupuytren
city: Lyon Cedex 08
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Insitut du Cancer
city: Saint-Herblain
country: France
facility: Institut de Cancérologie de l'Ouest - Site René Gauducheau
city: Strasbourg
country: France
facility: CHRU Strasbourg
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
References: