Clinical trial (study) comparing the efficacy and safety of mifamurtide versus standard treatment containing sorafenib in pediatric and young adult patients with high-risk osteosarcoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instytut Matki I Dziecka

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-04-20

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Agencja Badań Medycznych

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Diagnosis, Safety, Efficacy

Evaluation of clinical outcomes of treatment in the study patients, in particular event-free survival (EFS), and exploratory analysis of their relationship with molecular characteristics of the tumor

Secondary objectives 11

1. Assessment of the response rate (ORR), defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST v1.1.
2. Whole-exome sequencing analysis from blood (to detect germline variants) and tissue (fresh or frozen – to detect tissue-derived variants).
3. Liquid biopsy – analysis of circulating tumor DNA (ctDNA) from plasma to assess markers of baseline and acquired resistance in samples before treatment, during treatment, and at progression.
4. Gene expression profile analysis using RNA sequencing.
5. Single-cell profile analysis (20,000 cells – transcriptomes).
6. Analysis of programmed death ligand 1 (PD-L1) expression levels using immunohistochemistry (IHC), immune cell profiling, and other biomarkers where appropriate (GD2).
7. DNA methylation profiling/analysis.
8. High-throughput NGS analysis of FFPE material (tumor tissue).
9. Assessment of event-free survival (EFS) as the primary clinical endpoint, and assessment of progression-free survival (PFS) and overall survival (OS) as secondary endpoints.
10. Assessment of the safety and tolerability of the treatment.
11. Exploratory assessment of the relationship between clinical outcomes and tumor-specific biomarkers, molecular subtypes, and gene expression signatures assessed in archived tumor samples, paired tumor biopsies, and blood samples.

Conditions and MedDRA coding

Relapsed/refractory osteosarcoma, High-grade osteosarcoma

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age ≥ 5 years and ≤ 30 years at the time of study enrollment.
2. Osteosarcoma confirmed by histopathological examination based on previously performed tests.
3. Providing written, informed consent to participate in the study (including treatment with mifamurtide and sorafenib) in accordance with current legal regulations.
4. Patient classified as high-risk.
5. Life expectancy of at least 12 weeks from the date of signing the informed consent.
6. Patient deemed fit to receive systemic treatment.
7. Patient deemed able to swallow tablets.
8. Disease in complete remission or stable disease according to WHO criteria prior to randomization.
9. Completed surgery (major surgery ≥ 2 weeks) and radiotherapy (≥ 4 weeks) prior to IMP administration.
10. Recovery from adverse effects of prior surgery and/or radiotherapy.
11. Consent to use effective contraception throughout the study period and for at least 1 year after discontinuation of study treatment in patients at pubertal and sexual maturity.

Exclusion criteria 15

1. Failure to meet any of the inclusion criteria.
2. Prior treatment with mifamurtide.
3. Hypersensitivity to the study drug or any of its components (including mifamurtide and sorafenib).
4. Concomitant treatment with other drugs that may interact with mifamurtide or sorafenib or other cytotoxic agents.
5. Persistent toxicity related to prior therapy precludes treatment with mifamurtide or sorafenib.
6. Significant cardiac conduction abnormalities, including known familial long QT syndrome or a screening corrected QT interval (QTc) >480 ms.
7. Symptoms of congestive heart failure or left ventricular ejection fraction <50%.
8. Requirement or likely need for corticosteroids at doses >10 mg prednisolone (or equivalent) daily or other immunosuppressive medications.
9. Uncontrolled blood pressure (blood pressure values ​​not maintained within the recommended range (≥140/90 mmHg) despite treatment).
10. Arterial or venous thrombotic or embolic events, such as stroke (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism, within the last 6 months before the first study drug administration.
11. Active hepatitis B or C infection or chronic hepatitis B or C infection requiring antiviral therapy.
12. Any bleeding or hemorrhagic event ≥ CTCAE v5 grade 3 within 4 weeks before the first study drug administration.
13. Diagnosis of other malignancies prior to study enrollment.
14. Planning to become pregnant, being pregnant, or breastfeeding.
15. Other acute or persistent disorders, behaviors, or abnormal laboratory test results that may increase the risks associated with participation in this clinical trial or with the study drug, or that may affect the interpretation of the study results, or that, in the opinion of the investigator, disqualify the patient from participating in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. EFS (Event-Free Survival) – the time from randomization to the first event, i.e., death, disease progression, or disease relapse, whichever occurs first. Assessment will be conducted from the date of randomization to the date of the event or to the date of the last available assessment.

Secondary endpoints 4

1. OS (Overall Survival) – Overall survival will be measured from randomization to death from any cause; for patients alive at the end of follow-up, data will be censored at the date of last confirmed contact.
2. PFS (Progression-Free Survival) – Progression-free survival will be measured from randomization to the date of disease progression or death, whichever occurs first.
3. ORR (Overall Response Rate) – Response rate, defined as the percentage of patients with the best documented complete response (CR) or partial response (PR), assessed according to RECIST v1.1 at the time points specified in the imaging schedule.
4. Evaluation of the safety of mifamurtide in patients with osteosarcoma. Safety will be assessed based on the number of serious adverse events (SAEs), the number of adverse events (AEs), a physical examination with analysis of recorded vital signs and laboratory abnormalities according to NCI CTCAE v5.0, from the start of treatment to the end of safety follow-up according to the study schedule.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instytut Matki I Dziecka

Sponsor organisation

Instytut Matki I Dziecka

Address

Ul Marcina Kasprzaka 17 A

City

Warsaw

Postcode

01-211

Country

Poland

Scientific contact point

Organisation

Instytut Matki I Dziecka

Contact name

Prof. dr hab. n. med. Anna Raciborska

Public contact point

Organisation

Instytut Matki I Dziecka

Contact name

Project Manager

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications