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

NCT ID: NCT04698785

Last Updated: 2024-09-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-21

Study Completion Date

2026-07-21

Brief Summary

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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.

Detailed Description

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This is a multicenter phase II study.

Patients with evaluable unresectable residual disease will be accrued after they completed standard of care, consisting of:

* At diagnosis: standard multimodal treatment based on histological subtype
* At relapse: chemotherapy

Patients who meet the eligibility criteria will receive regorafenib + best supportive care (BSC) as maintenance treatment for a maximum 12 months period.

After their eligibility has been confirmed, patients will receive regorafenib until disease progression, or for a maximum of 12 months, or unacceptable toxicity or willingness to stop, whichever occurs first.

After the completion of the maintenance therapy (12 months) patients will be followed-up until the first radiological disease progression, unless a premature disease progression occurred. All patients will be followed-up until the data cut-off (12 months after the last inclusion).

The vital status will be updated once for all patients at 24 months after the last inclusion, based on patient's medical file.

Conditions

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Bone Sarcoma Osteosarcoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Regorafenib and best supportive care

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).

Group Type EXPERIMENTAL

Treatment by regorafenib and best supportive care

Intervention Type 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

Interventions

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Treatment by regorafenib and best supportive care

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

Intervention Type DRUG

Other Intervention Names

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Experimental arm

Eligibility Criteria

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Inclusion Criteria

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

I11. Patients, and their parents when applicable, must sign and date an informed consent document indicating that they have been informed of all the pertinent aspects of the trial prior to enrolment;

I12. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures;

I13. Patients affiliated to the Social Security System

I14. Body Surface Area (BSA) ≥ 1.30m² at the time of consenting to the study

Exclusion Criteria

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 :

1. No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the past 12 months prior to enrolment;
2. No history of AIDS-defining cancers (e.g. Kaposi's sarcoma, aggressive B-cell lymphoma and invasive cervical cancer);
3. Subjects should be on established anti-retroviral therapy for at least 4 weeks and have an HIV viral load of \< 400 copies/mL prior to enrolment;

E8. Active or chronic hepatitis B or C requiring treatment with antiviral therapy; Nota Bene: Subjects with a history of hepatitis B or C who have normal alanine aminotransferase (ALT) and are hepatitis B surface antigen negative and/or have undetectable HCV RNA are eligible

E9. Dehydration according to NCI-CTCAE v5 Grade \>1;

E10. Difficulties to swallow oral medication and/or any mal-absorption condition and/or any Gastrointestinal (GI) disease that may significantly alter the absorption of regorafenib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection);

E11. Patients with seizure disorder requiring medication;

E12. Concurrent enrolment in another clinical trial in which investigational therapies are administered;

E13. Known hypersensitivity to the active substance or to any of the excipients;

E14. Pregnant women, women who are likely to become pregnant or are breast-feeding. Women of childbearing potential must have a negative serum β-Human Chorionic Gonadotropin (HCG) pregnancy test within 7 days prior randomization;

E15. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;

E16. Patients with history of non-compliance to medical regimens or unwilling or unable to comply with the protocol;

E17. Interstitial lung disease with ongoing signs and symptoms at the time of informed consent;

E18. Non-healing wound, non-healing ulcer, or non-healing bone fracture;

E19. Patients with evidence or history of any bleeding diathesis, irrespective of severity;

E20. Any haemorrhage or bleeding event ≥ CTCAE v5 Grade 3 within 4 weeks prior to the first study drug administration;

E21. Clinically significant unrelated systemic illness (e.g., serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that would compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results;

E22. Patients using prohibited concomitant and/or concurrent medications (see section "Prohibited concomitant/concurrent treatments);

E23. Patients under tutorship or curatorship.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre Leon Berard

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mehdi BRAHMI

Role: PRINCIPAL_INVESTIGATOR

Centre Léon Bérard, Lyon

Locations

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Chu Besancon

Besançon, , France

Site Status NOT_YET_RECRUITING

Institut Bergonie

Bordeaux, , France

Site Status RECRUITING

Centre Georges Francois Leclerc

Dijon, , France

Site Status NOT_YET_RECRUITING

Centre Oscar Lambret

Lille, , France

Site Status NOT_YET_RECRUITING

Centre Leon Berard

Lyon, , France

Site Status RECRUITING

Hopital de La Timone

Marseille, , France

Site Status RECRUITING

Icm Val D'Aurelle

Montpellier, , France

Site Status NOT_YET_RECRUITING

Hotel Dieu Nantes

Nantes, , France

Site Status NOT_YET_RECRUITING

Institut Curie

Paris, , France

Site Status RECRUITING

Hôpital COCHIN

Paris, , France

Site Status RECRUITING

Ico Rene Gauducheau

Saint-Herblain, , France

Site Status RECRUITING

Chu Saint-Etienne

Saint-Priest-en-Jarez, , France

Site Status NOT_YET_RECRUITING

CHRU Hôpital Hautepierre

Strasbourg, , France

Site Status RECRUITING

ICANS

Strasbourg, , France

Site Status NOT_YET_RECRUITING

Iuct Oncopole

Toulouse, , France

Site Status RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status NOT_YET_RECRUITING

Countries

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France

Central Contacts

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Julien GAUTIER

Role: CONTACT

+33(0)426556829

Facility Contacts

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Loïc CHAIGNEAU

Role: primary

+33(0)3 81 66 81 66

Maud TOULMONDE

Role: primary

+ 33 (0)5 56 33 34 48

Alice HERVIEUX

Role: primary

+33 (0)3 80 73 75 06

Nicolas PENEL

Role: primary

+33(0)3 20 29 59 20

Mehdi BRAHMI

Role: primary

+33(0)4 78 78 59 73

Role: primary

+33(0)4 91 38 57 08

Nelly FIRMIN

Role: primary

+33(0)4 67 61 45 65

Morgane CLEIREC

Role: primary

+33 (0)2 40 08 36 10

Sophie PIPERNO-NEUMANN

Role: primary

+33 (0)1 44 32 46 72

Pascaline BOUDOU-ROUQUETTE

Role: primary

+33(0)1 58 41 14 39

Emmanuelle BOMPAS

Role: primary

+33(0)2 40 67 99 39

Claire BERGER

Role: primary

+33(0)4 77 82 88 08

Natacha ENTZ WERLE

Role: primary

+33(0)3 88 12 83 89

Justine GANTZER

Role: primary

+33(0)3 68 76 66 66

Thibaud VALENTIN

Role: primary

+33(0)5 31 15 51 70

Nathalie GASPAR

Role: primary

+33(0)1 42 11 43 16

Other Identifiers

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ET19000144 (REGOMAIN)

Identifier Type: -

Identifier Source: org_study_id

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