Evaluation of the Safety and Efficacy of Mifamurtide Versus Standard Treatment With Sorafenib in Patients With High-risk Osteosarcoma

Evaluation of the Safety and Efficacy of Mifamurtide Versus Standard Treatment With Sorafenib in Patients With High-risk Osteosarcoma (DRAGONFLY)

Prospective, open, interventional, randomized, non-commercial trial

The DRAGONFLY study includes:

1. Perform molecular and immunohistochemical studies from tumor tissue from biopsy or archival material.

2. Perform molecular tests from blood - ctDNA analysis (liquid biopsy).

3. Assess the stage of progression by performing standard tests to evaluate the extent of the disease and the capacity of the various organs

4. In patients classified in the high-risk group, modification of therapy. Patients will be randomly assigned in proportions (1:1) to the experimental (M) and standard (S) groups.

   The M (experimental) group will receive immunotherapy - mifamurtide along with standard conventional chemotherapy, and the S (standard) group will receive standard conventional treatment containing sorafenib.

5. Correlate the results of the obtained genetic tests with clinical data (preliminary assessment of the impact of mutations on the clinical picture, course of treatment and prognosis).

6. Comparison of the usefulness of molecular/immunohistochemical profile assessment as a prognostic factor with other recognized prognostic factors.

7. Conduct a reanalysis of patients according to the intention-to-treat (ITT) principle.

Inclusion Criteria:

Part I:

1. Age ≥ 5 to ≤ 30 years at the time of qualification.
2. Histopathologically confirmed osteosarcoma based on previous diagnostic tests.
3. Provision of written, informed consent to participate in the study, including treatment with mifamurtide and sorafenib, in accordance with current legal regulations, prior to the initiation of any study procedures.

Part II:

1. Participants of the Part I classified as high-risk.
2. Expected survival of at least 12 weeks from the time of signing informed consent.
3. Patient deemed capable of receiving systemic treatment.
4. Patient able to swallow tablets.
5. Disease in complete remission or stable disease per WHO criteria before randomization.
6. Major surgery performed ≥ 2 weeks and radiotherapy ≥ 4 weeks before inclusion in the mifamurtide group.
7. Recovery from adverse effects of prior surgery and/or radiotherapy.
8. Signed informed consent to participate in the study (including mifamurtide and sorafenib treatment) in accordance with applicable legal regulations.
9. Agreement to use effective contraception throughout the study period and for at least one year after discontinuing treatment for patients of reproductive age.

Exclusion Criteria:

1. Failure to meet any of the inclusion criteria.
2. Previous treatment with mifamurtide.
3. Hypersensitivity to the investigational drug or any of its components (including mifamurtide and sorafenib).
4. Concurrent treatment with drugs that may interact with mifamurtide, sorafenib, or other cytostatics.
5. Persistent toxicity from prior therapy that precludes treatment with mifamurtide or sorafenib.
6. Significant cardiac conduction abnormalities, including a known family history of long QT syndrome or a corrected QT interval (QTc) > 480 ms.
7. Symptoms of congestive heart failure or a left ventricular ejection fraction < 50%.
8. Need or probable need for corticosteroids at doses > 10 mg of prednisone (or equivalent) daily or other immunosuppressive drugs.
9. Uncontrolled blood pressure.
10. Arterial or venous thromboembolic events, such as stroke (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months before the first administration of the investigational drug.
11. Active hepatitis B or C or chronic hepatitis B or C requiring antiviral therapy.
12. Any bleeding or hemorrhagic event ≥ CTCAE v5 grade 3 within 4 weeks before the first administration of the investigational drug.
13. Diagnosis of other malignancies prior to study entry.
14. Pregnancy planning, current pregnancy, or breastfeeding.
15. Other acute or persistent disorders, behaviors, or abnormal laboratory results that may increase the risk associated with participation in this clinical study or receiving the investigational drug, may impact study results interpretation, or, in the investigator's opinion, disqualify the patient from study participation