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

Primary Purpose

Non-metastatic Soft-tissue Sarcoma, Resectable

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Doxorubicin
Ifosfamide or dacarbazine
Doxorubicin
Ifosfamide or dacarbazine
At the discretion of the investigator
Sponsored by
Institut Bergonié
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-metastatic Soft-tissue Sarcoma focused on measuring Solid tumor, Phase III trial, Soft-tissue sarcoma, Resectable, Non-metastatic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Institut BergonieRecruiting
  • Centre Georges François LeclercRecruiting
  • CHU DupuytrenRecruiting
  • Centre Léon BérardRecruiting
  • Institut Paoli CalmettesRecruiting
  • Insitut du CancerRecruiting
  • Institut de Cancérologie de l'Ouest - Site René GauducheauRecruiting
  • CHRU StrasbourgRecruiting
  • Institut Claudius RegaudRecruiting
  • Institut Gustave Roussy

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm A

Arm B

Prospective cohort

Arm Description

Control-Arm phase III high-risk CINSARC: Patients will be treated by doxorubicin (60 or 75mg/m² day or 20- or 25 mg/m² per day from day1 to day 3) + ifosfamide (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 of a 21-days cycle for up to 3 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).

Experimental-Arm phase III high-risk CINSARC: Patients will be treated by doxorubicin (60 or 75mg/m² day or 20 or 25 mg/m² per day from day1 to day 3) + ifosfamide (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 of a 21-days cycle for up to 6 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).

Patients will be treated at the discretion of the investigator

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
Overall survival in High-risk CINSARC patients
Overall survival (OS) defined as the time interval between the randomization date and the date of death.
Best overall response in High-risk CINSARC patients
Best overall response under treatment as per RECIST v1.1.
Histological response in High-risk CINSARC patients
Histological response defined as the proportion of recognizable cells on the tumor sample.
Safety profile in High-risk CINSARC patients
Toxicity graded using the common toxicity criteria from the NCI v5.
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).
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.
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.
Overall survival in Low-risk CINSARC patients
Overall survival defined as the time interval between the inclusion date and the date of death.

Full Information

First Posted
January 10, 2019
Last Updated
February 28, 2023
Sponsor
Institut Bergonié
Collaborators
Novartis, Chugai Pharma France
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1. Study Identification

Unique Protocol Identification Number
NCT03805022
Brief Title
Benefit of Intensified Peri-operative Chemotherapy Within High-risk CINSARC Patients With Resectable Soft-tissue Sarcomas
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 14, 2019 (Actual)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Bergonié
Collaborators
Novartis, Chugai Pharma France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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).
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-metastatic Soft-tissue Sarcoma, Resectable
Keywords
Solid tumor, Phase III trial, Soft-tissue sarcoma, Resectable, Non-metastatic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This is a multicenter trial with: An open randomized two-arm phase III trial for high-risk CINSARC patients assessing whether the addition of 3 additional neo-adjuvant cycles of chemotherapy (doxorubicin based chemotherapy) to standard management (3 cycles of neoadjuvant anthracycline based chemotherapy + surgery +/- radiotherapy) improves the outcome of patients a prospective cohort for low-risk CINSARC patients.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
351 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
Control-Arm phase III high-risk CINSARC: Patients will be treated by doxorubicin (60 or 75mg/m² day or 20- or 25 mg/m² per day from day1 to day 3) + ifosfamide (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 of a 21-days cycle for up to 3 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).
Arm Title
Arm B
Arm Type
Experimental
Arm Description
Experimental-Arm phase III high-risk CINSARC: Patients will be treated by doxorubicin (60 or 75mg/m² day or 20 or 25 mg/m² per day from day1 to day 3) + ifosfamide (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 of a 21-days cycle for up to 6 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).
Arm Title
Prospective cohort
Arm Type
Experimental
Arm Description
Patients will be treated at the discretion of the investigator
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ifosfamide or dacarbazine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ifosfamide or dacarbazine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
At the discretion of the investigator
Intervention Description
Drug at the discretion of the investigator.
Primary Outcome Measure Information:
Title
Metastasis progression-free survival in High-risk CINSARC patients
Description
Metastasis progression-free survival (M-PFS) defined as the time interval between the date of randomization and the date of death or distant progression.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Loco-regional relapse-free survival in High-risk CINSARC patients
Description
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.
Time Frame
3 years
Title
Progression-free survival in High-risk CINSARC patients
Description
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).
Time Frame
3 years
Title
Overall survival in High-risk CINSARC patients
Description
Overall survival (OS) defined as the time interval between the randomization date and the date of death.
Time Frame
3 years
Title
Best overall response in High-risk CINSARC patients
Description
Best overall response under treatment as per RECIST v1.1.
Time Frame
Throughout the treatment period, an average of 6 months
Title
Histological response in High-risk CINSARC patients
Description
Histological response defined as the proportion of recognizable cells on the tumor sample.
Time Frame
An average of 6 months
Title
Safety profile in High-risk CINSARC patients
Description
Toxicity graded using the common toxicity criteria from the NCI v5.
Time Frame
Throughout the treatment period, an average of 6 months
Title
Progression-free survival in Low-risk CINSARC patients
Description
Progression-free survival defined as the time interval between the randomization date and the date of death or progression (as per RECIST v1.1).
Time Frame
3 years
Title
Metastasis progression-free survival in Low-risk CINSARC patients
Description
Metastasis progression-free survival defined as the time interval between the inclusion date and the date of death or distant progression.
Time Frame
3 years
Title
Loco-regional progression-free survival in Low-risk CINSARC patients
Description
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.
Time Frame
3 years
Title
Overall survival in Low-risk CINSARC patients
Description
Overall survival defined as the time interval between the inclusion date and the date of death.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria : 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, Grade 2 or 3 according to the FNCLCC grading system, Available archived tumour sample for research purpose, Non-metastatic and resectable disease, No prior treatment for the disease under study, Age ≥ 18 years, Life expectancy ≥ 3 months, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1, 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, 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, Voluntarily signed and dated written informed consents prior to any study specific procedure, Patients with a social security in compliance with the French law. Exclusion Criteria : Soft-tissue sarcoma with the following histological subtypes: well-differentiated liposarcoma, alveolar soft-part sarcoma, dermatofibrosarcoma protuberans, clearcell sarcoma, embryonal and alveolar rhabdomyosarcoma, 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, Any other contraindication to anthracycline, ifosfamide or dacarbazine chemotherapy, Participation to a study involving a medical or therapeutic intervention in the last 28 days, Known infection with HIV, hepatitis B, or hepatitis C, Females who are pregnant or breast-feeding, 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, Individuals deprived of liberty or placed under legal guardianship, Unwillingness or inability to comply with the study protocol for any reason. Additional criteria for randomization : High-risk CINSARC signature, No more than two cycle of neo-adjuvant anthracycline-based chemotherapy before randomization.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Antoine ITALIANO, MD, PhD
Phone
+33 5.56.33.33.33
Email
a.italiano@bordeaux.unicancer.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Simone MATHOULIN-PELISSIER, MD, PhD
Email
m.mathoulin@bordeaux.unicancer.fr
Facility Information:
Facility Name
Institut Bergonie
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoine ITALIANO, MD, PhD
Email
a.italiano@bordeaux.unicancer.fr
First Name & Middle Initial & Last Name & Degree
Antoine ITALIANO
Facility Name
Centre Georges François Leclerc
City
Dijon
ZIP/Postal Code
21079
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolas ISAMBERT
First Name & Middle Initial & Last Name & Degree
Nicolas ISAMBERT, MD
Facility Name
CHU Dupuytren
City
Limoges
ZIP/Postal Code
87042
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valérie LEBRUN-LY, MD
First Name & Middle Initial & Last Name & Degree
Valérie LEBRUN-LY, MD
Facility Name
Centre Léon Bérard
City
Lyon Cedex 08
ZIP/Postal Code
69373
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Yves BLAY, MD, PhD
First Name & Middle Initial & Last Name & Degree
Jean-Yves BLAY, MD, PhD
Facility Name
Institut Paoli Calmettes
City
Marseille
ZIP/Postal Code
13273
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
François BERTUCCI, MD, PhD
First Name & Middle Initial & Last Name & Degree
François BERTUCCI, MD, PhD
Facility Name
Insitut du Cancer
City
Montpellier
ZIP/Postal Code
34298
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nelly FIRMIN, MD
Email
nelly.firmin@icm.unicancer.fr
First Name & Middle Initial & Last Name & Degree
Nelly FIRMIN, MD
Facility Name
Institut de Cancérologie de l'Ouest - Site René Gauducheau
City
Saint-Herblain
ZIP/Postal Code
44805
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emmanuelle BOMPAS, MD
First Name & Middle Initial & Last Name & Degree
Emmanuelle BOMPAS, MD
Facility Name
CHRU Strasbourg
City
Strasbourg
ZIP/Postal Code
67200
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Emmanuel KURTZ, MD, PhD
Email
je.kurtz@icans.eu
Facility Name
Institut Claudius Regaud
City
Toulouse
ZIP/Postal Code
31052
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christine CHEVREAU
Email
chevreau.christine@iuct-oncopole.fr
First Name & Middle Initial & Last Name & Degree
Christine CHEVREAU
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94800
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Axel LE CESNE, MD
First Name & Middle Initial & Last Name & Degree
Axel LE CESNE, MD

12. IPD Sharing Statement

Learn more about this trial

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

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