Regorafenib in Patients With Refractory Primary Bone Tumors

NCT05395741 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: Regbone
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Osteosarcoma; Ewing Sarcoma of Bone

Keywords

TKI; refractory bone tumors; osteosarcoma; Ewing sarcoma; targeted treatment; solid tumor

Outcome Measures

Primary Outcomes (4)

• EFS - (Event-Free Survival).

  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.

  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

  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

  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 Outcomes (9)

• PFS (Progression-Free Survival).

  Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.

• OS (Overall Survival).

  Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.

• ORR (Overall Response Rate).

  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.

  Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.

• Maximum serum concentration in steady state Cmaxs.

  Safety analyzes are planned in accordance with the schedule of intermediate analyzes, at least every 12 months.

Study Arms (2)

R1 - Regorafenib Arm

EXPERIMENTAL

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

R2 - Control Group

NO INTERVENTION

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.

Interventions

Regorafenib DRUG

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.

Also known as: Stivarga

R1 - Regorafenib Arm

Eligibility Criteria

• Age: 9 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age \>9 years ≤ 21 years.
• Histologically proven Ewing sarcoma or osteosarcoma.
• 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):
• progression on the I line or next, or
• relapse.
• Signing of informed consent for trial participation (including for Regorafenib treatment) according with current legal regulations.
• Life expectancy of at least 12 weeks from the time informed consent was signed.
• Possibility of swallowing the tablet.
• 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.

You may not qualify if:

• Previous treatment with Regorafenib.
• Pregnancy and breastfeeding.
• Hypersensitivity to the study drug or any of its ingredients.
• Simultaneous treatment with other drugs which might interact with Regorafenib.
• Persistent toxicity related to prior therapy, making it impossible to treat with Regorafenib.
• Patients with uncontrolled hypertension.
• Patients with diseases of the coagulation system.
• Patients with heart defects and / or cardiac arrhythmias requiring permanent treatment with antiarrhythmic drugs.
• 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.

Sponsors & Collaborators

• Institute of Mother and Child, Warsaw, Poland: lead
• Maria Sklodowska-Curie National Research Institute of Oncology: collaborator

Study Sites (2)

the Institute of Mother and Child

Warsaw, 01-211, Poland

Location

Maria Sklodowska-Curie National Research Institute of Oncology

Warsaw, 02-781, Poland

Location

Related Publications (9)

• Agulnik M, Attia S. Growing Role of Regorafenib in the Treatment of Patients with Sarcoma. Target Oncol. 2018 Aug;13(4):417-422. doi: 10.1007/s11523-018-0575-0.

  PMID: 29931504 RESULT

• Allard M, Khoudour N, Rousseau B, Joly C, Costentin C, Blanchet B, Tournigand C, Hulin A. Simultaneous analysis of regorafenib and sorafenib and three of their metabolites in human plasma using LC-MS/MS. J Pharm Biomed Anal. 2017 Aug 5;142:42-48. doi: 10.1016/j.jpba.2017.04.053. Epub 2017 May 1.

  PMID: 28494338 RESULT

• Berry V, Basson L, Bogart E, Mir O, Blay JY, Italiano A, Bertucci F, Chevreau C, Clisant-Delaine S, Liegl-Antzager B, Tresch-Bruneel E, Wallet J, Taieb S, Decoupigny E, Le Cesne A, Brodowicz T, Penel N. REGOSARC: Regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma-A quality-adjusted time without symptoms of progression or toxicity analysis. Cancer. 2017 Jun 15;123(12):2294-2302. doi: 10.1002/cncr.30661. Epub 2017 Mar 10.

  PMID: 28295221 RESULT

• Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Breder V, Gerolami R, Masi G, Ross PJ, Song T, Bronowicki JP, Ollivier-Hourmand I, Kudo M, Cheng AL, Llovet JM, Finn RS, LeBerre MA, Baumhauer A, Meinhardt G, Han G; RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Jan 7;389(10064):56-66. doi: 10.1016/S0140-6736(16)32453-9. Epub 2016 Dec 6.

  PMID: 27932229 RESULT

• Cardoso E, Mercier T, Wagner AD, Homicsko K, Michielin O, Ellefsen-Lavoie K, Cagnon L, Diezi M, Buclin T, Widmer N, Csajka C, Decosterd L. Quantification of the next-generation oral anti-tumor drugs dabrafenib, trametinib, vemurafenib, cobimetinib, pazopanib, regorafenib and two metabolites in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Apr 15;1083:124-136. doi: 10.1016/j.jchromb.2018.02.008. Epub 2018 Feb 8.

  PMID: 29544202 RESULT

• Davis KL, Fox E, Merchant MS, Reid JM, Kudgus RA, Liu X, Minard CG, Voss S, Berg SL, Weigel BJ, Mackall CL. Nivolumab in children and young adults with relapsed or refractory solid tumours or lymphoma (ADVL1412): a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2020 Apr;21(4):541-550. doi: 10.1016/S1470-2045(20)30023-1. Epub 2020 Mar 17.

  PMID: 32192573 RESULT

• Davis LE, Bolejack V, Ryan CW, Ganjoo KN, Loggers ET, Chawla S, Agulnik M, Livingston MB, Reed D, Keedy V, Rushing D, Okuno S, Reinke DK, Riedel RF, Attia S, Mascarenhas L, Maki RG. Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma. J Clin Oncol. 2019 Jun 1;37(16):1424-1431. doi: 10.1200/JCO.18.02374. Epub 2019 Apr 23.

  PMID: 31013172 RESULT

• Dirksen U, Brennan B, Le Deley MC, Cozic N, van den Berg H, Bhadri V, Brichard B, Claude L, Craft A, Amler S, Gaspar N, Gelderblom H, Goldsby R, Gorlick R, Grier HE, Guinbretiere JM, Hauser P, Hjorth L, Janeway K, Juergens H, Judson I, Krailo M, Kruseova J, Kuehne T, Ladenstein R, Lervat C, Lessnick SL, Lewis I, Linassier C, Marec-Berard P, Marina N, Morland B, Pacquement H, Paulussen M, Randall RL, Ranft A, Le Teuff G, Wheatley K, Whelan J, Womer R, Oberlin O, Hawkins DS; Euro-E.W.I.N.G. 99 and Ewing 2008 Investigators. High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008. J Clin Oncol. 2019 Dec 1;37(34):3192-3202. doi: 10.1200/JCO.19.00915. Epub 2019 Sep 25.

  PMID: 31553693 RESULT

• Duffaud F, Mir O, Boudou-Rouquette P, Piperno-Neumann S, Penel N, Bompas E, Delcambre C, Kalbacher E, Italiano A, Collard O, Chevreau C, Saada E, Isambert N, Delaye J, Schiffler C, Bouvier C, Vidal V, Chabaud S, Blay JY; French Sarcoma Group. Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2019 Jan;20(1):120-133. doi: 10.1016/S1470-2045(18)30742-3. Epub 2018 Nov 23.

  PMID: 30477937 RESULT

MeSH Terms

Conditions

Osteosarcoma; Bone Neoplasms; Sarcoma, Ewing

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases

Study Officials

• Anna Raciborska, Prof.

  the Institue of Mother and Child

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head od Department of Oncology and Surgical Oncology for Children and Youth; Prof. Ass. PhD MD

Study Record Dates

• First Submitted: May 5, 2022
• First Posted: May 27, 2022
• Study Start: April 28, 2022
• Primary Completion: September 12, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 25, 2026

Record last verified: 2025-04

Locations

PL (2)