Phase III trial investigating the potential benefit of intensified peri-operative Chemotherapy in patients with in high-risk CINSARC patients with resectable soft-tissue SARComas

Phase III trial investigating the potential benefit of intensified peri-operative Chemotherapy in patients with in high-risk CINSARC patients with resectable soft-tissue SARComas - CIRSARC

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-000186-36-FR

Enrollment

334

Registered

2018-07-09

Start date

2019-01-07

Completion date

Unknown

Last updated

2024-10-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Resectable, non-metastatic soft-tissue sarcoma (STS) MedDRA version: 20.0 Level: LLT Classification code 10039494 Term: Sarcoma NOS System Organ Class: 100000004864

Interventions

Trade Name: DOXORUBICINE Pharmaceutical Form: Solution for injection INN or Proposed INN: DOXORUBICIN CAS Number: 23214-92-8 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal

Eligibility

Sex/Gender

All

Inclusion 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 284 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50

Exclusion criteria

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 and Ifosfamide-based 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.

Design outcomes

Primary

Measure	Time frame
Main Objective: The primary objective of this trial is to investigate whether the addition of 3 additional neo-adjuvant cycles of chemotherapy (doxorubicin and ifosfamide) to standard management according to the ISG-STS 10-01 study (3 cycles of neoadjuvant doxorubicin and ifosfamide 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).;Secondary Objective: 1· In high-risk CINSARC patients with resectable non-metastatic STS: o Comparison of the two therapeutic strategies (6 cycles versus 3 cycles of neoadjuvant chemotherapy) in terms of additional efficacy outcomes: - Loco-regional relapse-free survival (LR-RFS, after 3 years of follow-up), - Progression-free survival (PFS, after 3 years of follow-up), - Overall survival (OS, after 3 years of follow-up) - Best overall response under treatment as per RECIST 1.1. - Histological response (based on tumour samples) o Comparison of the safety profile of the two therapeutic strategies. o Translational research: Assessment of the prognostic and predictive values of treatment efficacy (PFS, M-PFS, LR-RFS and OS, after 3 years of follow-up) of gene expression profiling. 2· In low-risk CINSARC patients with resectable non-metastatic STS: o Description of patients’ treatment o PFS, M-PFS, LR-RFS and OS, after 3 years of follow-up.;Primary end point(s): HIGH-RISK CINSARC PATIENTS: Metastasis progression-free survival (M-PFS) is defined as the time interval between the randomization date and the date of death (whatever the cause), or distant progression, whichever occurs first (DATECAN guidelines, Bellera et al. Annals Oncol 2014). LOW-RISK CINSARC PATIENTS: M-PFS, LR-RFS, PFS and OS will be defined as the endpoints listed for high-risk CINSARC patients, with the exception of the starting date, which will be the date of diagnosis. These endpoints will	—

Measure

Time frame

Main Objective: The primary objective of this trial is to investigate whether the addition of 3 additional neo-adjuvant cycles of chemotherapy (doxorubicin and ifosfamide) to standard management according to the ISG-STS 10-01 study (3 cycles of neoadjuvant doxorubicin and ifosfamide 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).;Secondary Objective: 1· In high-risk CINSARC patients with resectable non-metastatic STS: o Comparison of the two therapeutic strategies (6 cycles versus 3 cycles of neoadjuvant chemotherapy) in terms of additional efficacy outcomes: - Loco-regional relapse-free survival (LR-RFS, after 3 years of follow-up), - Progression-free survival (PFS, after 3 years of follow-up), - Overall survival (OS, after 3 years of follow-up) - Best overall response under treatment as per RECIST 1.1. - Histological response (based on tumour samples) o Comparison of the safety profile of the two therapeutic strategies. o Translational research: Assessment of the prognostic and predictive values of treatment efficacy (PFS, M-PFS, LR-RFS and OS, after 3 years of follow-up) of gene expression profiling. 2· In low-risk CINSARC patients with resectable non-metastatic STS: o Description of patients’ treatment o PFS, M-PFS, LR-RFS and OS, after 3 years of follow-up.;Primary end point(s): HIGH-RISK CINSARC PATIENTS: Metastasis progression-free survival (M-PFS) is defined as the time interval between the randomization date and the date of death (whatever the cause), or distant progression, whichever occurs first (DATECAN guidelines, Bellera et al. Annals Oncol 2014). LOW-RISK CINSARC PATIENTS: M-PFS, LR-RFS, PFS and OS will be defined as the endpoints listed for high-risk CINSARC patients, with the exception of the starting date, which will be the date of diagnosis. These endpoints will

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Secondary

Measure	Time frame
Secondary end point(s): · Loco-regional relapse-free survival (LR-RFS) is defined as the time interval between the randomization date and the date of death (whatever the cause), or loco-regional progression, whichever occurs first (DATECAN guidelines, Bellera et al. Annals Oncol 2015). Progression-free survival is defined as the time interval between the randomization date and the date of death (whatever the cause) or progression (as per RECIST v1.1), whichever occurs first. · Overall survival is defined as the time interval between the randomization date and the date of death (whatever the cause). · Best overall response is defined as the best response recorded from randomization until the end of neoadjuvant chemotherapy taking into account any requirement for confirmation as per RECIST v1.1 criteria. · Histological response is defined based on tumour sample as the average proportion of recognizable cells on the tumour sample [Huvos et al, Arch Pathol Lab Med 1977]. Good histological response is defined as <10% viable cells on the tumour sample. · Safety will be described using the common toxicity criteria from the NCI v5.;Timepoint(s) of evaluation of this end point: - LR-RFS, PFS, OS after 3 years of follow-up; - Best overall response: throughout the treatment period, an average of 6 months; - Histological response: on surgical sample, estimated within 5 months after treatment initiation; - Safety profile: throughout the treatment period, an average of 6 months; - Translational research: at baseline and on surgery sample.	—

Measure

Time frame

Secondary end point(s): · Loco-regional relapse-free survival (LR-RFS) is defined as the time interval between the randomization date and the date of death (whatever the cause), or loco-regional progression, whichever occurs first (DATECAN guidelines, Bellera et al. Annals Oncol 2015). Progression-free survival is defined as the time interval between the randomization date and the date of death (whatever the cause) or progression (as per RECIST v1.1), whichever occurs first. · Overall survival is defined as the time interval between the randomization date and the date of death (whatever the cause). · Best overall response is defined as the best response recorded from randomization until the end of neoadjuvant chemotherapy taking into account any requirement for confirmation as per RECIST v1.1 criteria. · Histological response is defined based on tumour sample as the average proportion of recognizable cells on the tumour sample [Huvos et al, Arch Pathol Lab Med 1977]. Good histological response is defined as <10% viable cells on the tumour sample. · Safety will be described using the common toxicity criteria from the NCI v5.;Timepoint(s) of evaluation of this end point: - LR-RFS, PFS, OS after 3 years of follow-up; - Best overall response: throughout the treatment period, an average of 6 months; - Histological response: on surgical sample, estimated within 5 months after treatment initiation; - Safety profile: throughout the treatment period, an average of 6 months; - Translational research: at baseline and on surgery sample.

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Countries

France

Contacts

Public ContactGeneral Manager

Institut Bergonié

f.mahon@bordeaux.unicancer.fr+33556333300

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026