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Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (SARCOME13)

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ClinicalTrials.gov Identifier: NCT03643133
Recruitment Status : Recruiting
First Posted : August 22, 2018
Last Update Posted : March 24, 2021
Sponsor:
Information provided by (Responsible Party):
UNICANCER

Brief Summary:
Trial evaluating the impact on efficacy of mifamurtide as add-on treatment to post-operative chemotherapy compared to post-operative chemotherapy alone in first-line treatment of patients with high-risk osteosarcoma (defined as metastatic osteosarcoma at diagnosis or localised osteosarcoma with poor histological response).

Condition or disease Intervention/treatment Phase
Osteosarcoma Drug: Mifamurtide Combination Product: EI or M-API regimen depending on patient age Phase 2

Detailed Description:

Multicentre, randomised, open-label, phase II trial, with 2 parallel groups. After pre-operative chemotherapy and surgery of the primary tumour and lung metastases (if applicable), patients presenting high-risk osteosarcoma (defined as metastatic osteosarcoma at diagnosis or localised osteosarcoma with poor histological response) will be randomised between 2 arms:

  • Control arm: post-operative chemotherapy alone (with regimens adapted to the age of patient)
  • Experimental arm : post-operative chemotherapy combined with mifamurtide

This randomised trial is part of a study recruiting all patients ≤50 years old with a newly diagnosed high-grade osteosarcoma.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicentre, Randomised, Phase 2 Trial of Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (Metastatic Osteosarcoma at Diagnosis or Localised Disease With Poor Histological Response)
Actual Study Start Date : October 23, 2018
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2028

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Control arm

Post-operative chemotherapy alone (EI or M-API regimen depending on patient age) :

M-API regimen (≤25 years) :

Doxorubicin 60 mg/m², Day 1 Ifosfamide 3 g/m² Day 1 and 2 Cisplatin 100 mg/m², Day 2

EI regimen (26-50 years) :

Etoposide 75 mg/m²/d, Day 1-4 Ifosfamide 3 g/m²/d, Day 1-4

Combination Product: EI or M-API regimen depending on patient age

M-API regimen:

One course of high-dose Methotrexate (optional) followed by 5 courses of API, every 21 days

EI regimen :

5 course of EI, every 21 days


Experimental: Experimental arm
Post-operative chemotherapy (EI or M-API regimen) combined with Mifamurtide 2 mg/m² twice weekly post-randomisation for 12 weeks then weekly for 24 weeks
Drug: Mifamurtide
48 doses overall over 36 weeks
Other Name: MEPACT

Combination Product: EI or M-API regimen depending on patient age

M-API regimen:

One course of high-dose Methotrexate (optional) followed by 5 courses of API, every 21 days

EI regimen :

5 course of EI, every 21 days





Primary Outcome Measures :
  1. Compare event-free survival in the treatment arms [ Time Frame: Expected average duration of 3 years from randomization ]
    Event-free survival defined as the time duration from randomisation to time of first event (loco-regional or distant relapse or progression, second malignancy, death from any cause)


Secondary Outcome Measures :
  1. Compare overall survival in the treatment arms [ Time Frame: Up to 10 years from randomization ]
    Overall survival defined as the time duration from randomisation to death, whatever the cause of death

  2. Compare actual and planned cumulative dose and dose intensity of mifamurtide [ Time Frame: Up to 36 weeks from randomization (until end of treatment) ]
    Calculation of actual cumulative dose and dose intensity compared to the planned treatment administration schedule

  3. Compare the incidence of adverse events in the treatment arms [ Time Frame: Up to 40 weeks from randomization (4 weeks after end of treatment) ]
    Evaluation of toxicity (graded by NCI-CTCAE v4)



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Registration Criteria:

  1. All newly diagnosed, biopsy-proven, high-grade osteosarcoma, whatever the initial extension of the disease
  2. Age >2 years and ≤50 years;
  3. Normal haematological, renal, cardiac and hepatic functions
  4. Planned neoadjuvant chemotherapy as follows:

    1. Methotrexate-Etoposide-Ifosfamide (M-EI regimen) for patients ≤25 years
    2. Doxorubicin-Cisplatin-Ifosfamide (API-AI regimen) for patients 26-50 years
  5. Written informed consent from patients and/or their parents/guardians before enrolment and any study-related procedure
  6. Affiliation to a social insurance regimen

Inclusion Criteria:

  1. Patient with a histologically proven, confirmed by experts pathologists panel (before surgery at the latest), high-grade osteosarcoma
  2. Registered at diagnosis into the study
  3. Primary tumour resected after pre-operative chemotherapy
  4. Osteosarcoma classified as high risk because of at least one risk factor:

    1. presence of distant metastases or skip metastases at diagnosis
    2. and/or poor histological response to pre-operative chemotherapy (>10% residual viable cells on the analysis of the primary tumour surgical specimen)
  5. Pre-operative chemotherapy combining

    1. Methotrexate-Etoposide-Ifosfamide (M-EI regimen) for patients ≤25 years
    2. Doxorubicin-Cisplatin-Ifosfamide (API-AI regimen) for patients 26-50 years
  6. Screening laboratory values must meet the following criteria (using CTCAE v4) and should be obtained within 7 days prior to randomisation:

    1. Absolute neutrophil count ≥1.0 x 10⁹/L
    2. Platelets ≥100 x 10⁹/L
    3. Haemoglobin ≥8.0 g/mL
    4. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN) in the absence of liver metastases or ≤5 x ULN in the presence of liver metastases
    5. Total Bilirubin ≤2 x ULN (except Gilbert Syndrome: <3.0 mg/dL) or Total Bilirubin ≤5.0 x ULN in the presence of liver metastases
    6. Creatinine clearance ≥60 mL/min/1.73 m² according to the Schwartz or Cockcroft formula according to patient's age
  7. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) done within 7 days prior to randomisation
  8. Provision of dated and signed written informed consent for the randomised trial prior to any study specific procedures, sampling and analyses.
  9. Patient fit to undergo protocol treatment and follow-up
  10. Affiliation to a social insurance regimen

Exclusion Criteria:

  1. Low grade osteosarcoma, parosteal or periosteal osteosarcoma
  2. Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 3 years.
  3. Osteosarcoma with multiple metastases for whom complete removal is not expected to be feasible even after shrinkage with chemotherapy
  4. Progressive disease at any site under initial chemotherapy, confirmed before randomisation time, and not totally resected during surgery
  5. Any medical condition precluding treatment with protocol chemotherapy
  6. Fractional Shortening <28% or left ventricular ejection fraction (LVEF) 50% before treatment (only for API post-operative chemotherapy) by echocardiogram or multigated acquisition (MUGA) scan
  7. Pregnancy or breast-feeding
  8. Hypersensitivity to the active substance or to any of the excipients
  9. Concurrent use of immunodepressive treatment such as cyclosporine, tacrolimus or other calcineurin inhibitors
  10. Concurrent use with high-dose non-steroidal anti-inflammatory drugs (NSAIDs, cyclooxygenase inhibitors)
  11. Inflammatory or auto-immune disease, allergy or asthma requiring a chronic use of steroid treatment that cannot be stopped.
  12. Patients with positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  13. Patients with positive tests for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection.

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): NCT03643133


Contacts
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Contact: Laure MONARD 33 (0)173797309 l-monard@unicancer.fr

Locations
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Sponsors and Collaborators
UNICANCER
Investigators
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Principal Investigator: Nathalie MD GASPAR, PhD Gustave Roussy Cancer Campus
Principal Investigator: Sophie MD PIPERNO-NEUMANN, PhD Institut Curie
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT03643133    
Other Study ID Numbers: UC-0150/1704
2017-001165-24 ( EudraCT Number )
First Posted: August 22, 2018    Key Record Dates
Last Update Posted: March 24, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual participant data will not be shared at an individual level, they will be part of the study database including all enrolled patients.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UNICANCER:
Bone
Neoplasm, bone tissue
Acetylmuramyl-Alanyl-Isoglutamine
Additional relevant MeSH terms:
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Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Mifamurtide
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs