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

Resectable Clinical Trial

— CIRSARC  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03805022
• Other study ID #: IB 2017-04
• Secondary ID: 2018-000186-36
• Status: Recruiting
• Phase: Phase 3
• Start date: February 14, 2019
• Est. completion date: February 2025

Study information

• Verified date: February 2023
• Source: Institut Bergonié
• Contact: Antoine ITALIANO, MD, PhD
• Phone: +33 5.56.33.33.33
• Email: a.italiano[@]bordeaux.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 351
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Non-metastatic Soft-tissue Sarcoma
• Resectable
• Sarcoma

Intervention

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 3 cycles.
• 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.
• 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.
• 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.
• At the discretion of the investigator
Drug at the discretion of the investigator.

Locations

Country	Name	City	State
France	Institut Bergonie	Bordeaux
France	Centre Georges François Leclerc	Dijon
France	CHU Dupuytren	Limoges
France	Centre Léon Bérard	Lyon Cedex 08
France	Institut Paoli Calmettes	Marseille
France	Insitut du Cancer	Montpellier
France	Institut de Cancérologie de l'Ouest - Site René Gauducheau	Saint-Herblain
France	CHRU Strasbourg	Strasbourg
France	Institut Claudius Regaud	Toulouse
France	Institut Gustave Roussy	Villejuif

Sponsors (3)

Lead Sponsor	Collaborator
Institut Bergonié	Chugai Pharma France, Novartis

Country where clinical trial is conducted

France, 

Outcome

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