Refractory primary bone tumors MedDRA version: 27.1 Level: PT Classification code 10015562 Term: Ewing's sarcoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 27.1 Level: PT Classification code 10015564 Term: Ewing's sarcoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 27.0 Level: PT Classification code 10031294 Term: Osteosarcoma meta
Conditions
Interventions
Trade Name: Stivarga 40 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Regorafenib
CAS Number: 755037-03-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Sponsors
Instytut Matki i Dziecka
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age> 9 years and = 21 years at the time of inclusion for the study. 2. Ewing's sarcoma or osteosarcoma confirmed by histopathological examination and the tests performed so far. 3. Treatment failure identified no earlier than 30 days prior to study treatment initiation (at least one subsection must be met for the patient to meet this criterion): a. progression on treatment of I or another line or b. relapse. 4. Giving written, informed consent to participate in the study prior to the commencement of the procedures included in the study protocol, including treatment with regorafenib in accordance with the current legal regulations. 5. Life expectancy of at least 12 weeks from signing the informed consent. 6. Possibility of swallowing the tablet. 7. Consent to use effective contraception throughout the period of regorafenib treatment and at least 2 years after its discontinuation in patients in puberty. Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Failure to meet any of the inclusion criteria. 2. Prior treatment with regorafenib. 3. Pregnancy and breastfeeding. 4. Known hypersensitivity to the drug or any of its ingredients. 5. Taking medications that cannot be used while under regorafenib treatment. 6. Persistent toxicity related to previous therapy, preventing drug incorporation. 7. Diagnosis of other neoplastic disease prior to inclusion in the study. 8. Patients with uncontrolled hypertension. 9. Patients with diseases related to the coagulation disorders. 10. Patients with heart defects and / or cardiac arrhythmias requiring permanent treatment with antiarrhythmic drugs. 11. Other acute or chronic medical conditions, behaviors, or abnormal laboratory values ??that may increase the risk of participating in this clinical trial or taking the study medication, or may affect the interpretation of the study results, or, in the investigator's opinion, may cause that the patient should not be enrolled in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy and safety of regorafenib in patients with refractory primary bone tumors;Secondary Objective: 1. Determination of the optimal dosing regimen of the test substance in patients from 9 years to 21 years through monitored pharmacokinetic parameters and pharmacodynamic effects. 2. To determine the safety of regorafenib treatment in patients with primary bone tumors refractory to conventional therapy, aged 9 to 21 years. 3. Determination of pharmacokinetic parameters Cmaxs, Cmins, Css, time to steady-state concentration. 4. Evaluation of clinical response to regorafenib treatment in terms of pharmacokinetics / serum drug concentration. 5. Assessment of adverse effects of regorafenib in terms of pharmacokinetics / serum drug concentration. 6. Assessment of the molecular profile in patients with primary bone tumors refractory to conventional therapy, aged 9 to 21 years. 7. Assessment of the molecular profile as a prognostic factor in comparison with other recognized factors. 8. Derivation of an immortalized cell line.;Primary end point(s): • EFS - (Event-Free Survival) event-free survival - will be measured from randomization to the occurrence of: death, assertion of disease progression or recurrence, finding a secondary neoplasm. • Determination of the dose of the test substance in patients between 9 and 18 years at which exposure to the drug similar to that recommended for adults will be achieved. • To evaluate the safety of regorafenib by analyzing adverse events (AEs) including adverse events of special importance. • Assessment of the safety of regorafenib through the analysis of recorded vital signs, laboratory test results, echocardiography, and ECG.;Timepoint(s) of evaluation of this end point: Throughout the study. Interim analyzes were scheduled at least every 12 months from the opening of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • PFS (Progression-Free Survival) - progression-free survival - will be measured from randomization to finding disease progression in imaging studies. • OS (Overall Survival) - will be measured from randomization to death due to neoplastic disease. • ORR (Overall Response Rate) - Percentage of patients who achieved a protocol-defined response to treatment. • Time to reach the target serum concentration of the test substance. • Maximum serum concentration at steady state Cmaxs. • Steady-state trough serum concentration Cminss. • Casual steady-state serum concentration Css. • Exposure to Ctau. • Time to steady-state concentration of the test substance in the serum.;Timepoint(s) of evaluation of this end point: Throughout the study. Interim analyzes were scheduled at least every 12 months from the opening of the study. | — |
Countries
Poland
Contacts
Public ContactSponsor Study Manager
Instytut Matki i Dziecka
Outcome results
None listed