Neoplasms

All Conditions

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Osteosarcoma

Sarcoma, Ewing

Bone Neoplasms

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Bone Diseases

Soft Tissue Sarcoma

Ewing Sarcoma

R1 - the experimental group. Standard oncological treatment will be started. Additionally, patients will receive regorafenib orally at doses adjusted for age, body surface area and pharmacokinetics. Treatment with regorafenib will be continued for up to 1 year or until disease progression, patient death, unacceptable toxicity, or study closure. Pharmacokinetics and safety profile of the investigational product (IP) will be determined throughout the course therapy.

R2 - the control group - will receive only standard treatment. In the event of progression or relapse, patients in the control group will have the option to receive the IP along with the standard treatment of the next line.

Patients will receive regorafenib orally at doses adjusted for age, body surface area and pharmacokinetics. Treatment with regorafenib will be continued for up to 1 year or until disease progression, patient death, unacceptable toxicity, or study closure. Pharmacokinetics and safety profile of the investigational product (IP) will be determined throughout the course therapy. In the event of progression or relapse, patients in the control group will have the option to receive the IP along with the standard treatment of the next line.

Regorafenib

Katarzyna Maleszewska

Katarzyna Maleszewska, mgr

Anna Raciborska, Prof.

DZIAŁ BADAŃ KLINICZNYCH

Piotr Rutkowski, Prof.

The aim of the project is to improve treatment outcomes in patients with primary malignant bone tumors, refractory to standard therapy, by increasing the availability of advanced therapy, as well as to develop treatment options using advanced molecular diagnostics for patients who have not responded to the standard therapeutic regimen, and to introduce modern diagnostics for risk stratification and for the use in molecularly targeted therapies.

The scope of the project is to cover the entire population of children, adolescents and young adults from the age of 9 to the age of 21, who progressed to first-line treatment or who presented with a recurrence of Ewing's sarcoma or osteosarcoma. Despite escalating doses of chemotherapy and radiotherapy, aggressive surgical procedures in patients with dissemination disease and negative prognostic factors, no improvement in treatment outcomes has been achieved for over 30 years. For this reason, other therapeutic options are being investigated. There have been no significant responses to immunotherapy. Although, the inclusion of tyrosine kinase inhibitors (TKIs) appears to be promising.

The identification of new mutations in bone tumors has led to a better insight into the molecular basis of these tumors, which has resulted in a more significant role of genetic research in everyday practice. Although traditional histopathological examinations are currently the basis for the diagnosis of bone tumors, the developing techniques of molecular biology make it possible, in many cases, to refine the diagnosis and, in the near future, will become the basis for the classification of these neoplasms. Moreover, these technics are expected to enable the qualification of patients to modern molecularly targeted therapies.

Based on the above data, the objectives of the project are as follows: 1. to estimate the nature and frequency of mutations in the tumor tissue, 2. to compare molecular test results with clinical data (which will allow for the initial assessment of the impact of the mutation status on the clinical condition, course of treatment and prognosis), 3. to include targeted treatment - broad spectrum tyrosine kinase inhibitor - regorafenib in standard therapy.

Regorafenib in Patients With Refractory Primary Bone Tumors

Evaluation of the Efficacy and Safety of Regorafenib in Patients With Refractory Primary Bone Tumors

To explore the efficacy in terms of EFS - (Event-Free Survival)

Safety will be assessed by the rate of participants presenting with Adverse Events stratified by grade, category, affected organ or system, as number of serious adverse events (SAEs)

Safety will be assessed by the rate of participants presenting with Adverse Events stratified by grade, category, affected organ or system, as number of adverse events (AEs), including adverse events of special interest

Safety will be assessed by analyzing recorded vital signs, laboratory test results, echocardiography, and ECG.

progression-free survival - will be measured from randomization to the detection of disease progression in imaging tests.

overall survival - will be measured from randomization to death due to cancer.

the percentage of patients who achieved the response to treatment defined in the protocol.

Concentration parameters will come directly from the concentration values measured in PK samples.

by monitoring the patient's clinical and molecular status

Spots Global Cancer Trial Database for refractory bone tumors