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Sarcome-13/OS2016 trial protocol: a multicentre, randomised, open-label, phase II trial of mifamurtide combined with postoperative chemotherapy for patients with newly diagnosed high-risk osteosarcoma.
- Source :
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BMJ open [BMJ Open] 2019 May 19; Vol. 9 (5), pp. e025877. Date of Electronic Publication: 2019 May 19. - Publication Year :
- 2019
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Abstract
- Introduction: The controversial results on the mifamurtide efficacy associated with chemotherapy, issued from the American INT-0133-study, in localised osteosarcomas, and the underpowered analysis performed separately in metastatic patients, should be clarified to homogenise international use of this promising drug. The European Commission has granted a marketing authorisation to mifamurtide combined with postoperative chemotherapy in localised osteosarcomas but not in metastatic patients, while the Food and Drug Administration (FDA) has denied this authorisation.<br />Methods and Analysis: Sarcome-13/OS2016 trial is a multicentre randomised open-label phase II trial evaluating the survival benefit of mifamurtide administered during 36 weeks in combination with postoperative chemotherapy versus chemotherapy alone, in patients >2 and ≤50 years with newly diagnosed high-risk localised or metastatic osteosarcoma. The main objective is to evaluate the impact on event-free survival (EFS) of mifamurtide on intention-to-treat population. The secondary objectives are to evaluate the impact of mifamurtide on overall survival, to evaluate the feasibility and toxicity of the planned treatment, to correlate biology/immunology with the mifamurtide efficacy/toxicity. With a total of 126 enrolled patients and 51 events, the power is 80% if mifamurtide is associated with an 18% improvement of the 3-year EFS (52%vs70%, equivalent to an HR=0.55), with a one-sided logrank test alpha=10%. As relevant historical data are available (aggregate treatment effect from the INT-0133 trial and individual data from the control group of the Sarcome-09/OS2006 trial), a Bayesian analysis is also planned.<br />Ethics and Dissemination: This study was approved by the 'Comité de Protection des Personnes Ile de France I' (12/06/2018), complies with the Declaration of Helsinki and French laws and regulations, and follows the International Conference on Harmonisation E6 Guideline for Good Clinical Practice. The trial results, even if they are inconclusive, as well as biological ancillary studies will be presented at appropriate international congresses and published in international peer-review journals.<br />Trial Registration Number: EudraCT 2017-001165-24, NCT03643133.<br />Competing Interests: Competing interests: None declared.<br /> (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Subjects :
- Acetylmuramyl-Alanyl-Isoglutamine therapeutic use
Clinical Trials, Phase II as Topic
France
Humans
Multicenter Studies as Topic
Neoadjuvant Therapy
Osteosarcoma mortality
Osteosarcoma surgery
Postoperative Care
Randomized Controlled Trials as Topic
Survival Analysis
Acetylmuramyl-Alanyl-Isoglutamine analogs & derivatives
Immunologic Factors therapeutic use
Osteosarcoma drug therapy
Phosphatidylethanolamines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 2044-6055
- Volume :
- 9
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- BMJ open
- Publication Type :
- Academic Journal
- Accession number :
- 31110092
- Full Text :
- https://doi.org/10.1136/bmjopen-2018-025877