Regorafenib in Patients With Refractory Primary Bone Tumors (Regbone)

January 12, 2024 updated by: Anna Raciborska, Institute of Mother and Child, Warsaw, Poland

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Poland
      • Warsaw, Poland, 02-781
        • Recruiting
        • Maria Sklodowska-Curie National Research Institute of Oncology
        • Contact:
        • Principal Investigator:
          • Piotr Rutkowski, Prof.
      • Warsaw, Poland, 01-211
        • Recruiting
        • the Institute of Mother and Child
        • Contact:
        • Principal Investigator:
          • Anna Raciborska, Prof.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

9 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: R1 - Regorafenib Arm
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.
Drug: Regorafenib
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.
Other Names:
  • Stivarga
No Intervention: R2 - Control Group
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
EFS - (Event-Free Survival).
Time Frame: 1 year
To explore the efficacy in terms of EFS - (Event-Free Survival)
1 year
Determining the dose of the test substance in patients between 9 and 21 years of age, at which exposure to the drug will be similar to that recommended for adults.
Time Frame: 1 year
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)
1 year
Assessment of safety in terms of AEs
Time Frame: from date of randomization, until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months.
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
from date of randomization, until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months.
Assessment of the safety of regorafenib
Time Frame: from date of randomization, until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months.
Safety will be assessed by analyzing recorded vital signs, laboratory test results, echocardiography, and ECG.
from date of randomization, until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS (Progression-Free Survival).
Time Frame: Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
progression-free survival - will be measured from randomization to the detection of disease progression in imaging tests.
Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
OS (Overall Survival).
Time Frame: Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
overall survival - will be measured from randomization to death due to cancer.
Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
ORR (Overall Response Rate).
Time Frame: Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
the percentage of patients who achieved the response to treatment defined in the protocol.
Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
Time to achieving sufficient drug concentration in serum.
Time Frame: Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
Concentration parameters will come directly from the concentration values measured in PK samples.
Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
Maximum serum concentration in steady state Cmaxs.
Time Frame: Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
Concentration parameters will come directly from the concentration values measured in PK samples.
Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
Minimum serum concentration in steady state Cminss.
Time Frame: Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
Concentration parameters will come directly from the concentration values measured in PK samples.
Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
Random serum concentration in steady state Css.
Time Frame: Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
Concentration parameters will come directly from the concentration values measured in PK samples.
Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
Drug exposure Ctau.
Time Frame: Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
by monitoring the patient's clinical and molecular status
Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
Time to achieving steady state drug concentration in serum.
Time Frame: Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.
by monitoring the patient's clinical and molecular status
Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Mother and Child, Warsaw, Poland

Collaborators

Maria Sklodowska-Curie National Research Institute of Oncology

Investigators

  • Principal Investigator: Anna Raciborska, Prof., the Institue of Mother and Child

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 28, 2022

Primary Completion (Estimated)

September 12, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

May 5, 2022

First Submitted That Met QC Criteria

May 24, 2022

First Posted (Actual)

May 27, 2022

Study Record Updates

Last Update Posted (Actual)

January 17, 2024

Last Update Submitted That Met QC Criteria

January 12, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Regbone

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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