Interest of peri operative CHemotherapy In patients with CINSARC highrisk localized Soft Tissue Sarcoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oncopole Claudius Regaud

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Oct 2020 → ongoing

Decision date (initial)

2024-06-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Direction Générale de l'Offre de Soins (DGOS)

External identifiers

EU CT number

2024-515384-62-00

EudraCT number

2019-003014-13

ClinicalTrials.gov

NCT04307277

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary objective of this study is 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.

Secondary objectives 2

1. To compare the two therapeutics strategies in high-risk CINSARC patients with resectable soft-tissue sarcoma (STS), in terms of: Disease-free survival, Overall survival, Safety profile.
2. To prospectively validate the prognostic value of CINSARC signature in STS treated by standard treatment.

Conditions and MedDRA coding

Soft Tissue Sarcoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 1.Diagnosis of soft-tissue sarcoma, histologically confirmed by RRePS (Réseau de Référence en Pathologie des Sarcomes et des Viscères) network
2. 2.According to FNCLCC grading system, grade 1, 2 or 3 tumors
3. 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. 4.6 weeks or less between surgical excision and inclusion (if performed before inclusion)
5. 5.Available archived FFPE tumor sample in sufficient quantity to allow CINSARC qualification
6. 6.Age ≥ 18 years
7. 7.Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
8. 8.Life expectancy of at least 12 weeks after the start of the treatment
9. 9. 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 (ifosfamide treatment) or 6 months (dacarbazine treatment) after the end of the treatment period. All non-menopaused women should have a negative pregnancy test within 72 hours prior to registration. Men should accept to use an effective contraception during treatment period and at least 3 months after the end of the study treatment.
10. 10.Signed written informed consent
11. 11.Patient affiliated to a Social Health Insurance in France
12. 1.High-risk CINSARC signature (FOR THE RANDOMIZED PHASE III STUDY)
13. 2.Acceptable hematologic function (within 72 hours prior randomization): Absolute neutrophil count (ANC) ≥ 1.5 G/L, Platelet count ≥ 100 G/L and Hemoglobin > 9g/dL
14. 3.Acceptable renal function within 72 hours prior randomization: Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min (by the Cockcroft and Gault formula)
15. 4.Acceptable liver function: Bilirubin ≤ 1.5 x upper limit of normal (ULN), AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN
16. 5.Normal LVEF (>50%) measured by echocardiography or isotopic ventriculography

Exclusion criteria 15

1. 1.Soft-tissue sarcoma with the following histological subtypes: welldifferentiated liposarcomas, alveolar soft-part sarcoma, dermatofibrosarcoma protuberans, clear-cell sarcoma, epithelioid sarcoma, alveolar or embryonal rhabdomyosarcoma
2. 2.Primitive cutaneous, retroperitoneal, uterus or visceral STS
3. 3.Metastatic disease
4. 4.Previous or ongoing treatment for the sarcoma (with the exception of surgical excision)
5. 5.Contra-indication for Doxorubicin, Ifosfamide and Dacarbazine treatments
6. 6.Prior therapy with ifosfamide or cyclophosphamide or other nitrogen mustards, and prior therapy with anthracyclines
7. 7.Prior mediastinal/cardiac radiotherapy
8. 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. 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. 10.Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
11. 11.Known infection with HIV, hepatitis B, or hepatitis C
12. 12.Women who are breastfeeding, pregnant or who plan to become pregnant while in the trial
13. 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. 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. 15.Patient unable to comply with the protocol for any reason

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is Metastasis-free survival (MFS). MFS is defined by the delay between randomization and the appearance of metastatic disease or death from any cause.

Secondary endpoints 3

1. Disease-free survival (DFS) is defined by the delay between randomization and first relapse (local, regional, or distant) or death from any cause. Patients still alive at the time of analysis (including lost to follow-up) without appearance of relapse will be censored at the last disease assessment date.
2. Overall survival (OS) is defined by the delay between randomization and death from any cause. Patients still alive at the time of analysis (including lost to follow-up) will be censored at the last known alive date.
3. Safety will be assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v5.0).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oncopole Claudius Regaud

Sponsor organisation

Oncopole Claudius Regaud

Address

1 Avenue Irene Joliot Curie

City

Toulouse

Postcode

31100

Country

France

Scientific contact point

Organisation

Oncopole Claudius Regaud

Contact name

Dr Thibaud VALENTIN

Public contact point

Organisation

Oncopole Claudius Regaud

Contact name

Muriel MOUNIER

Locations

1 EU/EEA country · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications