To evaluate the efficacy and safety of regorafenib in patients with refractory primary bone tumors.

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]

Trial duration

29 Apr 2022 → ongoing

Decision date (initial)

2024-08-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-514720-17-00

EudraCT number

2021-005339-22

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy, Efficacy

To evaluate the efficacy and safety of regorafenib in patients with refractory primary bone tumors

Secondary objectives 7

1. To determine the safety of regorafenib treatment in patients with primary bone tumors refractory to conventional therapy, aged 9 to 21 years.
2. Determination of pharmacokinetic parameters Cmaxs, Cmins, Css, time to steady-state concentration.
3. Evaluation of clinical response to regorafenib treatment in terms of pharmacokinetics / serum drug concentration.
4. Assessment of adverse effects of regorafenib in terms of pharmacokinetics / serum drug concentration.
5. Assessment of the molecular profile in patients with primary bone tumors refractory to conventional therapy, aged 9 to 21 years.
6. Assessment of the molecular profile as a prognostic factor in comparison with other recognized factors.
7. Derivation of an immortalized cell line.

Conditions and MedDRA coding

Refractory primary bone tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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.

Exclusion criteria 11

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. 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.
2. 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.
3. To evaluate the safety of regorafenib by analyzing adverse events (AEs) including adverse events of special importance.
4. Assessment of the safety of regorafenib through the analysis of recorded vital signs, laboratory test results, echocardiography, and ECG.

Secondary endpoints 9

1. PFS (Progression-Free Survival) - progression-free survival - will be measured from randomization to finding disease progression in imaging studies.
2. OS (Overall Survival) - will be measured from randomization to death due to neoplastic disease.
3. ORR (Overall Response Rate) - Percentage of patients who achieved a protocol-defined response to treatment.
4. Time to reach the target serum concentration of the test substance.
5. Maximum serum concentration at steady state Cmaxs.
6. Steady-state trough serum concentration Cminss.
7. Casual steady-state serum concentration Css.
8. Exposure to Ctau.
9. Time to steady-state concentration of the test substance in the serum.

Investigational products

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

Test 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

Klinika Onkologii i Chirurgii Onkologicznej Dzieci i Młodzieży IMID

Public contact point

Organisation

Instytut Matki I Dziecka

Contact name

Klinika Onkologii i Chirurgii Onkologicznej Dzieci i Młodzieży IMID

Third parties 5

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 8 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