Interest of Peri Operative CHemotherapy In Patients With CINSARC High-risk Localized Soft Tissue Sarcoma

Soft Tissue Sarcoma Clinical Trial

— CHIC-STS01  

Official title:

Interest of Peri Operative CHemotherapy In Patients With CINSARC High-risk Localized Soft Tissue Sarcoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04307277
• Other study ID #: 19SARC05
• Status: Recruiting
• Phase: Phase 3
• Start date: October 9, 2020
• Est. completion date: March 2025

Study information

• Verified date: February 2024
• Source: Institut Claudius Regaud
• Contact: Thibaud VALENTIN
• Phone: 05 31 15 51 70
• Email: valentin.thibaud[@]iuct-oncopole.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase III, multicenter, randomized open-label and comparative study designed to demonstrate whether adding 4 cycles of peri-operative doxorubicin-based chemotherapy improves metastasis-free survival as compared with standard management in patients with resectable STS, considered as high-risk according to CINSARC (Complexity Index in SARComas) signature.

After signed informed consent, patients considered as eligible to CHIC-STS study by the investigator will be enrolled in the study and a molecular screening will be performed (600 patients will be screened).

Patients considered as low-risk according to CINSARC signature will be treated at the discretion of the clinicians (prospective cohort).

Patients considered as high-risk according to CINSARC signature will be randomized in the open-label multicenter phase III trial and assigned in one of the two following treatments arms:

• Arm A (control arm): Standard of care (surgical excision +/- external radiotherapy).

• Arm B (experimental arm): Standard of care + 4 cycles of intravenous chemotherapy during 12 weeks.

A total of 250 patients will have to be randomized with 125 patients in each arm.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Diagnosis of soft-tissue sarcoma, histologically confirmed by RRePS (Réseau de Référence en Pathologie des Sarcomes et des Viscères) network.

2. According to FNCLCC grading system, grade 1, 2 or 3 tumors.

3. Resectable and localized disease after appropriate extension work-up (including at least a chest-CT).

4. Available archived FFPE tumor sample in sufficient quantity to allow CINSARC qualification.

5. Age = 18 years.

6. Eastern Cooperative Oncology Group (ECOG) performance status = 2.

7. Life expectancy of at least 12 weeks after the start of the treatment.

8. Women should be post-menopaused or willing to accept the use of an effective contraceptive regimen during the treatment period and at least 12 months after the end of the treatment period. All non-menopaused women should have a negative pregnancy test within 72 hours prior to registration.

9. Signed written informed consent.

10. Patient affiliated to a Social Health Insurance in France.

Exclusion Criteria:

1. Soft-tissue sarcoma with the following histological subtypes: well-differentiated liposarcomas, alveolar soft-part sarcoma, dermatofibrosarcoma protuberans, clear-cell sarcoma, epithelioid sarcoma, alveolar or embryonal rhabdomyosarcoma.

2. Primitive cutaneous, retroperitoneal, uterus or visceral STS.

3. Metastatic disease.

4. Previous or ongoing treatment for the sarcoma (with the exception of a surgery for diagnosis intend).

5. Contra-indication for Doxorubicin, Ifosfamide and Dacarbazine treatments.

6. Prior therapy with ifosfamide or cyclophosphamide or other nitrogen mustards, and prior therapy with anthracyclines.

7. Prior mediastinal/cardiac radiotherapy.

8. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia, myocardial infarction within 6 months prior to study entry.

9. 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.

10. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.

11. Known infection with HIV, hepatitis B, or hepatitis C.

12. Women who are breastfeeding, pregnant or who plan to become pregnant while in the trial.

13. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.

14. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice).

15. Patient unable to comply with the protocol for any reason.

ADDITIONAL CRITERIA FOR THE RANDOMIZED PHASE III STUDY

1. High-risk CINSARC signature.

2. Acceptable hematologic function (within 72 hours of eligibility assessment): Absolute neutrophil count (ANC) = 1.5 G/L, Platelet count = 100 G/L and Hemoglobin > 9g/dL.

3. Acceptable renal function within 72 hours of eligibility assessment: Serum creatinine = 1.5 x ULN or calculated creatinine clearance = 60 mL/min (by the Cockcroft and Gault formula).

4. Acceptable liver function: Bilirubin = 1.5 x upper limit of normal (ULN), AST (SGOT) and ALT (SGPT) = 2.5 x ULN.

5. Normal LVEF (>50%) measured by echocardiography or isotopic ventriculography .

Related Conditions & MeSH terms

• Sarcoma
• Soft Tissue Sarcoma

Intervention

Drug:
• Standard of care + chemotherapy
Doxorubicine with Ifosfamide during 4 cycles Q3W Or Doxorubicine with Dacarbazine during 4 cycles Q3W (for patients with Leiomyosarcoma)

Other:
• Standard of care
Surgical excision with external radiotherapy (if applicable)

Locations

Country	Name	City	State
France	CHRU Besançon	Besançon
France	Institut Bergonié	Bordeaux
France	Centre François Baclesse	Caen
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Georges-François Leclerc	Dijon
France	CHU Grenoble	Grenoble
France	CHU Limoges	Limoges
France	Centre Léon Bérard	Lyon
France	CHU Marseille	Marseille
France	Institut Paoli-Calmettes	Marseille
France	Institut de Cancérologie de Montpellier	Montpellier
France	Centre Antoine Lacassagne	Nice
France	Hôpital Cochin	Paris
France	CHU Poitiers	Poitiers
France	Institut Godinot	Reims
France	Centre Eugène Marquis	Rennes
France	Centre Henri Becquerel	Rouen
France	CHU de SAINT ETIENNE	Saint-Étienne
France	Institut de Cancérologie de l'Ouest	Saint-Herblain
France	Institut de Cancérologie Strasbourg Europe	Strasbourg
France	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse
France	Institut de Cancérologie de Lorraine - Centre Alexis Vautrin	Vandœuvre-lès-Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Institut Claudius Regaud

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metastasis-free survival defined by the delay between randomization and the appearance of metastatic.		5 years for each patient
Secondary	Disease-free survival defined by the delay between randomization and first relapse (local, regional, or distant) or death from any cause.		5 years for each patient
Secondary	Safety assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v5.0).		4 months for each patient
Secondary	Overall survival defined by the delay between randomization and death from any cause.		5 years for each patient