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

• Sponsor: UNICANCER (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03643133
• Collaborator: (none)
• Enrollment: 126
• Locations: 31
• Arms: 2
• Anticipated Duration (Months): 119.3
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• Anticipated 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: Oct 23, 2018
• Anticipated Primary Completion Date: Oct 1, 2022
• Anticipated Study Completion Date: Oct 1, 2028

Arms and Interventions

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 Names: 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

Outcome Measures

Primary Outcome Measures

1. Compare event-free survival in the treatment arms [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 [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 [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 [Up to 40 weeks from randomization (4 weeks after end of treatment)]

   Evaluation of toxicity (graded by NCI-CTCAE v4)

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

5. Methotrexate-Etoposide-Ifosfamide (M-EI regimen) for patients ≤25 years

6. Doxorubicin-Cisplatin-Ifosfamide (API-AI regimen) for patients 26-50 years

7. Written informed consent from patients and/or their parents/guardians before enrolment and any study-related procedure

8. 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:

5. presence of distant metastases or skip metastases at diagnosis

6. and/or poor histological response to pre-operative chemotherapy (>10% residual viable cells on the analysis of the primary tumour surgical specimen)

7. Pre-operative chemotherapy combining

8. Methotrexate-Etoposide-Ifosfamide (M-EI regimen) for patients ≤25 years

9. Doxorubicin-Cisplatin-Ifosfamide (API-AI regimen) for patients 26-50 years

10. Screening laboratory values must meet the following criteria (using CTCAE v4) and should be obtained within 7 days prior to randomisation:

11. Absolute neutrophil count ≥1.0 x 10⁹/L

12. Platelets ≥100 x 10⁹/L

13. Haemoglobin ≥8.0 g/mL

14. 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

15. 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

16. Creatinine clearance ≥60 mL/min/1.73 m² according to the Schwartz or Cockcroft formula according to patient's age

17. 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

18. Provision of dated and signed written informed consent for the randomised trial prior to any study specific procedures, sampling and analyses.

19. Patient fit to undergo protocol treatment and follow-up

20. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHU Amiens-Picardie - Service d'oncologie hématologie pédiatrique	Amiens		France
2	CHU d'Angers - Service d'oncologie pédiatrique	Angers		France
3	Institut Bergonié - Service d'oncologie médicale	Bordeaux		France
4	CHU de Caen - Service d'oncologie hématologie pédiatrique	Caen		France
5	CHU de Grenoble - Service d'oncologie hématologie pédiatrique	La Tronche		France
6	Centre Oscar Lambret - Unité d'onco-pédiatrie	Lille		France
7	Centre Léon Bérard - IHOPE	Lyon		France
8	Centre Léon Bérard - Service d'oncologie médicale	Lyon		France
9	Hôpital de la Timone - service d'oncologie médicale	Marseille		France
10	Hôpital de la Timone - Service d'oncologie pédiatrique	Marseille		France
11	CHU Arnaud de Villeneuve - Onco-hématologie pédiatrique	Montpellier		France
12	Institut régional du Cancer de Montpellier - Service d'oncologie médicale	Montpellier		France
13	CHU de Nantes - Service d'oncologie hématologie pédiatrique	Nantes		France
14	CHU de Nice - Service d'oncologie hématologie pédiatrique	Nice		France
15	Institut Curie - Service d'oncologie médicale	Paris		France	75000
16	Hôpital Armand Trousseau - Service d'hématologie et d'oncologie pédiatrique	Paris		France
17	Hôpital Cochin	Paris		France
18	Institut Curie - Service d'oncologie pédiatrique	Paris		France
19	Centre Eugène Marquis - Service d'oncologie médicale	Rennes		France
20	Hôpital Charles Nicolle - Hémato-Immuno-Oncologie Pédiatrique	Rouen		France
21	Institut de Cancérologie de l'Ouest (Site René Gauducheau) - Service d'oncologie médicale	Saint-Herblain		France
22	Hôpital de Hautepierre - Onco-hématologie adulte	Strasbourg		France
23	Hôpital Hautepierre - Onco-hématologie pédiatrique	Strasbourg		France
24	CHU Toulouse - Hôpital des Enfants - Service d'Hémato-Immuno-Oncologie	Toulouse		France
25	Institut Claudius Regaud - service d'oncologie médicale	Toulouse		France
26	CHU Bretonneau - Service d'oncologie médicale	Tours		France
27	Hôpital Clocheville - Hématologie et oncologie pédiatrique	Tours		France
28	CHRU de Nancy - Onco-hématologie pédiatrique	Vandœuvre-lès-Nancy		France
29	Institut de Cancérologie de Lorraine - Service d'oncologie médicale	Vandœuvre-lès-Nancy		France
30	Institut Gustave Roussy - Service de cancérologie de l'enfant et de l'adolescent	Villejuif		France	94800
31	Institut Gustave Roussy - Service d'oncologie médicale	Villejuif		France

Sponsors and Collaborators

• UNICANCER

Investigators

• Principal Investigator: Nathalie MD GASPAR, PhD, Gustave Roussy Cancer Campus
• Principal Investigator: Sophie MD PIPERNO-NEUMANN, PhD, Institut Curie

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: UNICANCER
• ClinicalTrials.gov Identifier: NCT03643133
• Other Study ID Numbers: UC-0150/1704; 2017-001165-24
• First Posted: Aug 22, 2018
• Last Update Posted: Mar 16, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: Osteosarcoma; Mifamurtide

Study Results

No Results Posted as of Mar 16, 2022