Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 24 for:    sarcoma | Recruiting, Not yet recruiting, Available Studies | Interventional Studies | Phase 3

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03805022
Recruitment Status : Not yet recruiting
First Posted : January 15, 2019
Last Update Posted : January 15, 2019
Sponsor:
Collaborators:
Novartis
Chugai Pharma France
Information provided by (Responsible Party):
Institut Bergonié

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Non-metastatic Soft-tissue Sarcoma Resectable Drug: Doxorubicin Drug: Ifosfamide Drug: At the discretion of the investigator Phase 3

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 and ifosfamide based chemotherapy + surgery +/- radiotherapy)
  • Arm B: experimental arm (6 cycles of neoadjuvant doxorubicin and ifosfamide based chemotherapy + surgery +/- radiotherapy)

For low-risk CINSARC patients, this a multicenter prospective cohort with treatment at the discretion of the investigator.


Layout table for study information
Study Type : Interventional
Estimated Enrollment : 334 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 and ifosfamide) to standard management (3 cycles of neoadjuvant anthracycline and ifosfamide based chemotherapy + surgery +/- radiotherapy) improves the outcome of patients
  • a prospective cohort for low-risk CINSARC patients.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : February 2019
Estimated Primary Completion Date : February 2025
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A

Control-Arm phase III high-risk CINSARC:

Patients will be treated by doxorubicin (60-75mg/m² day or 20-25 mg/m² per day from day1 to day 3) + ifosfamide (7,5-9 g/m² over 3 days with mesna and G-CSF) 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).

Drug: Doxorubicin
A treatment cycle consists of 3 weeks. Doxorubicin will be administered from day 1 to day 3 (60-75mg/m² day or 20-25 mg/m² per day), repeated every 3 weeks, up to 3 cycles.

Drug: Ifosfamide
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), repeated every 3 weeks, up to 3 cycles.

Experimental: Arm B

Experimental-Arm phase III high-risk CINSARC:

Patients will be treated by doxorubicin (60-75mg/m² day or 20-25 mg/m² per day from day1 to day 3) + ifosfamide (7,5-9 g/m² over 3 days with mesna and G-CSF) 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).

Drug: Doxorubicin
A treatment cycle consists of 3 weeks. Doxorubicin will be administered from day 1 to day 3 (60-75mg/m² day or 20-25 mg/m² per day), repeated every 3 weeks, up to 6 cycles.

Drug: Ifosfamide
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), repeated every 3 weeks, up to 6 cycles.

Experimental: Prospective cohort
Patients will be treated at the discretion of the investigator
Drug: At the discretion of the investigator
Drug at the discretion of the investigator.




Primary Outcome Measures :
  1. Metastasis progression-free survival in High-risk CINSARC patients [ Time Frame: 3 years ]
    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 :
  1. Loco-regional relapse-free survival in High-risk CINSARC patients [ Time Frame: 3 years ]
    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.

  2. Progression-free survival in High-risk CINSARC patients [ Time Frame: 3 years ]
    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).

  3. Overall survival in High-risk CINSARC patients [ Time Frame: 3 years ]
    Overall survival (OS) defined as the time interval between the randomization date and the date of death.

  4. Best overall response in High-risk CINSARC patients [ Time Frame: Throughout the treatment period, an average of 6 months ]
    Best overall response under treatment as per RECIST v1.1.

  5. Histological response in High-risk CINSARC patients [ Time Frame: An average of 6 months ]
    Histological response defined as the proportion of recognizable cells on the tumor sample.

  6. Safety profile in High-risk CINSARC patients [ Time Frame: Throughout the treatment period, an average of 6 months ]
    Toxicity graded using the common toxicity criteria from the NCI v5.

  7. Progression-free survival in Low-risk CINSARC patients [ Time Frame: 3 years ]
    Progression-free survival defined as the time interval between the randomization date and the date of death or progression (as per RECIST v1.1).

  8. Metastasis progression-free survival in Low-risk CINSARC patients [ Time Frame: 3 years ]
    Metastasis progression-free survival defined as the time interval between the inclusion date and the date of death or distant progression.

  9. Loco-regional progression-free survival in Low-risk CINSARC patients [ Time Frame: 3 years ]
    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.

  10. Overall survival in Low-risk CINSARC patients [ Time Frame: 3 years ]
    Overall survival defined as the time interval between the inclusion date and the date of death.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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.

Additional criteria for randomization :

  1. High-risk CINSARC signature,
  2. No more than one cycle of neo-adjuvant anthracycline-based chemotherapy before randomization.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03805022


Contacts
Layout table for location contacts
Contact: Antoine ITALIANO, MD, PhD +33 5.56.33.33.33 a.italiano@bordeaux.unicancer.fr
Contact: Simone MATHOULIN-PELISSIER, MD, PhD m.mathoulin@bordeaux.unicancer.fr

Locations
Layout table for location information
France
Institut Bergonie Not yet recruiting
Bordeaux, France, 33076
Contact: Antoine ITALIANO, MD, PhD       a.italiano@bordeaux.unicancer.fr   
Principal Investigator: Antoine ITALIANO         
Centre Georges François Leclerc Not yet recruiting
Dijon, France, 21079
Contact: Nicolas ISAMBERT         
Principal Investigator: Nicolas ISAMBERT, MD         
CHU Dupuytren Not yet recruiting
Limoges, France, 87042
Contact: Valérie LEBRUN-LY, MD         
Principal Investigator: Valérie LEBRUN-LY, MD         
Centre Léon Bérard Not yet recruiting
Lyon Cedex 08, France, 69373
Contact: Jean-Yves BLAY, MD, PhD         
Principal Investigator: Jean-Yves BLAY, MD, PhD         
Institut Paoli Calmettes Not yet recruiting
Marseille, France, 13273
Contact: François BERTUCCI, MD, PhD         
Principal Investigator: François BERTUCCI, MD, PhD         
Insitut du Cancer Not yet recruiting
Montpellier, France, 34298
Contact: Nelly FIRMIN, MD         
Principal Investigator: Nelly FIRMIN, MD         
Institut Curie Not yet recruiting
Paris, France, 75005
Contact: Sophie PIPERNO-NEUMANN, MD         
Principal Investigator: Sophie PIPERNO-NEUMANN, MD         
Institut de Cancérologie de l'Ouest - Site René Gauducheau Not yet recruiting
Saint-Herblain, France, 44805
Contact: Emmanuelle BOMPAS, MD         
Principal Investigator: Emmanuelle BOMPAS, MD         
Institut Claudius Regaud Not yet recruiting
Toulouse, France, 31052
Contact: Christine CHEVREAU         
Principal Investigator: Christine CHEVREAU         
Institut Gustave Roussy Not yet recruiting
Villejuif, France, 94800
Contact: Axel LE CESNE, MD         
Principal Investigator: Axel LE CESNE, MD         
Sponsors and Collaborators
Institut Bergonié
Novartis
Chugai Pharma France

Layout table for additonal information
Responsible Party: Institut Bergonié
ClinicalTrials.gov Identifier: NCT03805022     History of Changes
Other Study ID Numbers: IB 2017-04
2018-000186-36 ( EudraCT Number )
First Posted: January 15, 2019    Key Record Dates
Last Update Posted: January 15, 2019
Last Verified: January 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Institut Bergonié:
Solid tumor
Phase III trial
Soft-tissue sarcoma
Resectable
Non-metastatic

Additional relevant MeSH terms:
Layout table for MeSH terms
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Doxorubicin
Liposomal doxorubicin
Ifosfamide
Isophosphamide mustard
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents