Brief Title
Regorafenib in Patients With Refractory Primary Bone Tumors
Official Title
Evaluation of the Efficacy and Safety of Regorafenib in Patients With Refractory Primary Bone Tumors
Brief Summary
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.
Detailed Description
The scope of the project is to cover the entire population of children, adolescents and young
adults from the age of 2 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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
EFS - (Event-Free Survival).
Secondary Outcome
PFS (Progression-Free Survival).
Condition
Osteosarcoma
Intervention
Regorafenib
Study Arms / Comparison Groups
R1 - Regorafenib Arm
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
30
Start Date
April 28, 2022
Completion Date
December 31, 2025
Primary Completion Date
September 12, 2025
Eligibility Criteria
Inclusion Criteria:
1. Age >9 years ≤ 21 years.
2. Histologically proven Ewing sarcoma or osteosarcoma.
3. Failure of the treatment identified no earlier than 30 days prior to study treatment
initiation (at least one of below needs to apply in order for this requirement to be
satisfied):
1. progression on the I line or next, or
2. relapse.
4. Signing of informed consent for trial participation (including for Regorafenib
treatment) according with current legal regulations.
5. Life expectancy of at least 12 weeks from the time informed consent was signed.
6. Possibility of swallowing the tablet.
7. Consent to the use of effective contraception throughout the period of the study and a
minimum of 2 year after discontinuation of study treatment in patients at puberty and
sexual maturity.
Exclusion Criteria:
1. Lack of inclusion criteria
2. Previous treatment with Regorafenib.
3. Pregnancy and breastfeeding.
4. Hypersensitivity to the study drug or any of its ingredients.
5. Simultaneous treatment with other drugs which might interact with Regorafenib.
6. Persistent toxicity related to prior therapy, making it impossible to treat with
Regorafenib.
7. Diagnosis of other malignancies before study inclusion.
8. Patients with uncontrolled hypertension.
9. Patients with diseases of the coagulation system.
10. Patients with heart defects and / or cardiac arrhythmias requiring permanent treatment
with antiarrhythmic drugs.
11. Other acute or persistent disorders, behaviors or abnormal laboratory test results,
which might increase the risk related to the participation in this clinical trial or
to taking the study drug, or which might influence the interpretation of the study
results, or which, in the investigator's opinion, disqualify a patient from
participating in the trial.
Gender
All
Ages
9 Years - 21 Years
Accepts Healthy Volunteers
No
Contacts
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Location Countries
Poland
Location Countries
Poland
Administrative Informations
NCT ID
NCT05395741
Organization ID
Regbone
Responsible Party
Principal Investigator
Study Sponsor
Institute of Mother and Child, Warsaw, Poland
Collaborators
Maria Sklodowska-Curie National Research Institute of Oncology
Study Sponsor
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Verification Date
May 2022