Phase Iii Trial Investigating Benefit of Intensified Peri-Operative Chemotherapy Within High-Risk Cinsarc Patients with Resectable Soft-Tissue Sarcomas

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Bergonie

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Feb 2019 → ongoing

Decision date (initial)

2024-02-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509489-39-00

EudraCT number

2018-000186-36

ClinicalTrials.gov

NCT03805022

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Pharmacogenomic, Pharmacodynamic

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).

Secondary objectives 2

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.

Conditions and MedDRA coding

Resectable, non-metastatic soft-tissue sarcoma (STS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

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 9

1. Soft-tissue sarcoma with the following histological subtypes: well-differentiated liposarcoma, alveolar soft-part sarcoma, dermatofibrosarcoma protuberans, clear-cell 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,
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 5

1. 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.
2. Overall survival is defined as the time interval between the randomization date and the date of death (whatever the cause).
3. 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
4. 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.
5. Safety will be described using the common toxicity criteria from the NCI v5.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Bergonie

Sponsor organisation

Institut Bergonie

Address

229 Cours De L Argonne

City

Bordeaux

Postcode

33000

Country

France

Scientific contact point

Organisation

Institut Bergonie

Contact name

Pr Antoine Italiano

Public contact point

Organisation

Institut Bergonie

Contact name

Aurore Barthod Malat

Locations

1 EU/EEA country · 11 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 9 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