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

Osteosarcoma Clinical Trial

— SARCOME13  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03643133
• Other study ID #: UC-0150/1704
• Secondary ID: 2017-001165-24
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 23, 2018
• Est. completion date: October 2033

Study information

• Verified date: February 2024
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: October 2033
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 50 Years

Eligibility

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 10?/L

2. Platelets =100 x 10?/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.

Related Conditions & MeSH terms

• Osteosarcoma

Intervention

Drug:
• Mifamurtide
48 doses overall over 36 weeks

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

Locations

Country	Name	City	State
France	CHU Amiens-Picardie - Service d'oncologie hématologie pédiatrique	Amiens
France	CHU d'Angers - Service d'oncologie pédiatrique	Angers
France	Institut Bergonié - Service d'oncologie médicale	Bordeaux
France	CHU de Caen - Service d'oncologie hématologie pédiatrique	Caen
France	CHU de Grenoble - Service d'oncologie hématologie pédiatrique	La Tronche
France	Centre Oscar Lambret - Unité d'onco-pédiatrie	Lille
France	Centre Léon Bérard - IHOPE	Lyon
France	Centre Léon Bérard - Service d'oncologie médicale	Lyon
France	Hôpital de la Timone - service d'oncologie médicale	Marseille
France	Hôpital de la Timone - Service d'oncologie pédiatrique	Marseille
France	CHU Arnaud de Villeneuve - Onco-hématologie pédiatrique	Montpellier
France	Institut régional du Cancer de Montpellier - Service d'oncologie médicale	Montpellier
France	CHU de Nantes - Service d'oncologie hématologie pédiatrique	Nantes
France	CHU de Nice - Service d'oncologie hématologie pédiatrique	Nice
France	Hôpital Armand Trousseau - Service d'hématologie et d'oncologie pédiatrique	Paris
France	Hôpital Cochin	Paris
France	Institut Curie - Service d'oncologie médicale	Paris
France	Institut Curie - Service d'oncologie pédiatrique	Paris
France	Centre Eugène Marquis - Service d'oncologie médicale	Rennes
France	Hôpital Charles Nicolle - Hémato-Immuno-Oncologie Pédiatrique	Rouen
France	Institut de Cancérologie de l'Ouest (Site René Gauducheau) - Service d'oncologie médicale	Saint-Herblain
France	Hôpital de Hautepierre - Onco-hématologie adulte	Strasbourg
France	Hôpital Hautepierre - Onco-hématologie pédiatrique	Strasbourg
France	CHU Toulouse - Hôpital des Enfants - Service d'Hémato-Immuno-Oncologie	Toulouse
France	Institut Claudius Regaud - service d'oncologie médicale	Toulouse
France	CHU Bretonneau - Service d'oncologie médicale	Tours
France	Hôpital Clocheville - Hématologie et oncologie pédiatrique	Tours
France	CHRU de Nancy - Onco-hématologie pédiatrique	Vandœuvre-lès-Nancy
France	Institut de Cancérologie de Lorraine - Service d'oncologie médicale	Vandœuvre-lès-Nancy
France	Institut Gustave Roussy - Service d'oncologie médicale	Villejuif
France	Institut Gustave Roussy - Service de cancérologie de l'enfant et de l'adolescent	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare event-free survival in the treatment arms	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)	Expected average duration of 3 years from randomization
Secondary	Compare overall survival in the treatment arms	Overall survival defined as the time duration from randomisation to death, whatever the cause of death	Up to 10 years from randomization
Secondary	Compare actual and planned cumulative dose and dose intensity of mifamurtide	Calculation of actual cumulative dose and dose intensity compared to the planned treatment administration schedule	Up to 36 weeks from randomization (until end of treatment)
Secondary	Compare the incidence of adverse events in the treatment arms	Evaluation of toxicity (graded by NCI-CTCAE v4)	Up to 40 weeks from randomization (4 weeks after end of treatment)