Efficacy of Regorafenib Combined With Best Supportive Care as Maintenance Treatment in High Grade Bone Sarcomas Patients

NCT04698785 | Recruiting Phase 2 DMC

• 1 other identifier: ET19000144 (REGOMAIN)
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 16

Brief Summary

This is a multicenter phase II study concerning patients with high-grade bone sarcoma (HGBS) without complete remission after standard treatment at diagnosis or at relapse. Patients will be treated with regorafenib + best supportive care (BSC) for a maximum of 12 months as maintenance therapy after standard line therapy completion. Progression free rate (PFR) data will be collected and analysed for all included patients to evaluate if regorafenib + BSC can be considered as an interesting treatment for further investigations in this indication.

Conditions

Bone Sarcoma; Osteosarcoma

Keywords

Bone sarcoma; Osteosarcoma; Maintenance therapy; Regorafenib; Progression-free rate; Objective response rate; Disease control rate; Overall survival; Quality of life; Tolerance; Tyrosine inhibitor kinase; Multitarget inhibitor; High-grade; Progression-Free survival

Outcome Measures

Primary Outcomes (1)

• Progression-Free Rate at 4 months (4m-PFR)

  The Progression-Free Rate at 4 months (4m-PFR) will be defined as the proportion of patients with a complete response, a partial response or stable disease, confirmed on tumour assessments according to the RECIST V1.1 at 4 months (16 weeks) after the date of regorafenib + BSC treatment initiation. Patients with a non-progressive disease at 16 ± 2 weeks after the date of regorafenib + BSC treatment initiation will be considered as "success" patients. Patients with a progressive disease and patients who died from any cause at 16 ± 2 weeks after the date of regorafenib + BSC treatment initiation will be considered as "failure" patients. At the time of analysis, if at least 18 "successes" are observed among the 36 analyzed patients, the regorafenib + BSC treatment will be considered as interesting for further investigations in this indication.

  Up to 16 weeks after the date of regorafenib + BSC treatment initiation

Secondary Outcomes (7)

• Progression-Free Survival (PFS)

  Up to 3 years

• Objective Response Rate (ORR)

  Up to 3 years

• Disease Control Rate (DCR) at 2 months

  2 months

• Disease Control Rate (DCR) at 4 months

  4 months

• Overall Survival (OS)

  Up to 3 years

Study Arms (1)

Regorafenib and best supportive care

EXPERIMENTAL

Treatment will be divided in 28 days cycles, including a 21-day period of treatment by regorafenib and best supportive care followed by a 7-day period of rest. In case of toxicity, dose can be reduced or treatment interrupted according to Specific Product Characteristics (SPC). Patients can receive up to a maximum of 13 cycles (maximum treatment period : 12 Months).

Drug: Treatment by regorafenib and best supportive care

Interventions

Treatment by regorafenib and best supportive care DRUG

Treatment for 13 cycles (12 months) maximum. During each cycle : * patients ≥ 16 years old and patients \<16 old with Body Surface Area (BSA) ≥ 1,70 m2 will take 3 tablets, once a day, corresponding to a total of 120 mg Regorafenib, during 21 days, followed by 7 days without treatment. * patients \< 16 years old with a 1,30 m2 ≤ BSA ≥ 1,70 m2 will take 2 tablets, once a day, corresponding to a total of 80 mg Regorafenib, during 21 days, followed by 7 days without treatment

Also known as: Experimental arm

Regorafenib and best supportive care

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• I1. Age ≥ 12 years at the day of consenting to the study;
• I2. Patients must have histologically confirmed high-grade sarcomas of bone primary localisation, including but not limited to: Osteosarcomas, Ewing sarcomas, Chondrosarcomas, Undifferenciated Pleomorphic Sarcomas (UPS), Leiomyosarcomas (LMS) and Angiosarcomas
• I3. Evaluable residual disease not amenable to resection after multimodal treatment principles either at diagnosis (after standard multimodal treatment based on the histological subtype) or at relapse (chemotherapy)
• I4. Non progressive disease (defined by the investigator according to the RECIST version 1.1 Appendix 1) at study entry;
• I5. Interval between the date of last anticancer treatment (chemotherapy or surgery) and the start date of regorafenib: at least 4 weeks but no longer than 2 months;
• I6. Life expectancy of greater than 6 months;
• I7. Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky ≥ 70%) (Appendix 2);
• I8. Adequate bone marrow and organ function defined by the following laboratory results:
• a. Bone marrow: i. Absolute neutrophil count ≥ 1.5 Giga/l ii. Platelets ≥ 100 Giga/l iii. Haemoglobin≥ 9 g/dl
• b. Hepatic function: i. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x Upper Limit of Normal (ULN) (≤ 5.0 × ULN for patients with liver involvement of their cancer) ii. Bilirubin ≤1.5 X ULN iii. Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x ULN in patient with liver involvement of their cancer). If Alkaline phosphatase \> 2.5 ULN, hepatic isoenzymes 5-nucleotidase or gamma-glutamyltransferase (GGT) tests must be performed; hepatic isoenzymes 5-nucleotidase must be within the normal range and/or GGT \< 1.5 x ULN.
• c. Renal function: i. Serum creatinine ≤ 1.5 x ULN ii. Glomerular Filtration Rate (GFR) ≥ 30 ml/min/1.73m2 according to the Modified Diet in Renal Disease (MDRD) abbreviated formula iii. Spot urine must not show ≥ 1 "+" protein in urine or the patient will require a repeat urine analysis. If repeat urinalysis shows 1 "+" protein or more, a 24-hour urine collection will be required and must show total protein excretion \< 1000 mg/24 hours
• d. Coagulation: International Normalized Ratio (INR)/Partial Thromboplastin Time (PTT) ≤1.5 x ULN; Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care;
• e. Pancreatic function: Lipase ≤ 1.5 x ULN
• I9. Recovery to anticancer-treatment related NCI-CTCAE v5 Grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug/procedure related toxicity (except alopecia, anaemia, and hypothyroidism);
• I10. Women of childbearing potential and male patients must agree to use adequate contraception (including at least the use of condoms) for the duration of treatment and for 7 months (210 days) in women of childbearing potential or 4 months (120 days) in men sexually active with women of childbearing potential after the last dose of regorafenib

You may not qualify if:

• E1. Prior treatment with any VEGFR inhibitor (thus, any prior exposure to regorafenib, sunitinib, sorafenib, pazopanib, bevacizumab, or other VEGFR inhibitor);
• E2. All soft tissue sarcomas (including but not limited to soft tissue osteosarcoma), and chordomas;
• E3. Prior history of malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) within 3 years prior to randomization;
• E4. Cardiovascular dysfunction defined by:
• Left ventricular ejection fraction (LVEF) \< 50%,
• Congestive heart failure ≥ New York Heart Association (NYHA) class 2,
• Myocardial infarction \< 6 months prior to first study drug administration,
• Cardiac arrhythmias requiring therapy (beta blockers or digoxin are permitted),
• Unstable (angina symptoms at rest) or new-onset angina within the last 3 months prior to first study drug administration;
• Uncontrolled hypertension (systolic blood pressure \> 150 mm Hg or diastolic pressure \> 90 mm Hg despite optimal treatment);
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the last 6 months before the first study drug administration;
• E5. Major surgical procedure, open biopsy or significant traumatic injury within 28 days before the first study drug administration;
• E6. Ongoing infection \> Grade 2 according to NCI-CTCAE v5;
• E7. Known history of human immunodeficiency virus infection;
• Nota Bene: Subjects with diagnosed human immunodeficiency virus (HIV) are eligible to participate in the study if they meet the following criteria :

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (16)

Chu Besancon

Besançon, 25030, France

NOT YET RECRUITING

Institut Bergonie

Bordeaux, 33076, France

RECRUITING

Centre Georges Francois Leclerc

Dijon, 21079, France

NOT YET RECRUITING

Centre Oscar Lambret

Lille, 59020, France

NOT YET RECRUITING

Centre Leon Berard

Lyon, 69373, France

RECRUITING

Hopital de La Timone

Marseille, 13385, France

RECRUITING

Icm Val D'Aurelle

Montpellier, 34298, France

NOT YET RECRUITING

Hotel Dieu Nantes

Nantes, 44093, France

NOT YET RECRUITING

Institut Curie

Paris, 75005, France

RECRUITING

Hôpital COCHIN

Paris, 75014, France

RECRUITING

Ico Rene Gauducheau

Saint-Herblain, 44805, France

RECRUITING

Chu Saint-Etienne

Saint-Priest-en-Jarez, 42270, France

NOT YET RECRUITING

CHRU Hôpital Hautepierre

Strasbourg, 67098, France

RECRUITING

ICANS

Strasbourg, 67200, France

NOT YET RECRUITING

Iuct Oncopole

Toulouse, 31059, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94805, France

NOT YET RECRUITING

MeSH Terms

Conditions

Bone Neoplasms; Osteosarcoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Mehdi BRAHMI

  Centre Léon Bérard, Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julien GAUTIER

CONTACT

+33(0)426556829; julien.gautier@lyon.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2021
• First Posted: January 7, 2021
• Study Start: July 21, 2021
• Primary Completion (Estimated): July 21, 2026
• Study Completion (Estimated): July 21, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

FR (16)