Detail Article

Informations générales (source: ClinicalTrials.gov)

Numéro NCT

NCT04055220 En recrutement IDF

Titre

A Randomized, Placebo-controlled, Double-blinded, Multicentre Study Evaluating the Efficacy and Safety of Regorafenib as Maintenance Therapy After First-line Treatment in Patients With Bone Sarcomas (REGOSTA)

Type

Interventional

Pathologie

Chondrosarcome
Hémangiosarcome
Léiomyosarcome
Sarcomes
Sarcome d'Ewing
Ostéosarcome
Histiocytome fibreux malin

Phase

N/A

Promoteur

Centre Leon Berard (Voir sur ClinicalTrials)

Date de début

mars 2020

Date de fin

octobre 2026

Dernière mise à jour

20 septembre 2024

Résumé

This is a randomized, double-blinded, 2 arms study concerning patients with bone sarcoma after the first line therapy. In the first arm, patients will be treated with regorafenib for a maximum of 12 months as maintenance therapy after first line therapy, whereas in the second arm, patients will be treated with placebo (standard of care). The comparison between this two arms will allow to determine whether or not regorafenib is efficient for disease control, in terms of Relapse-Free Survival improvement.

Détail

Voir le détail Bone sarcomas are rare primary bone cancers, although, their frequency has been increasing by 0.3% per year over the last decade. They include a very large number of tumour types belonging to the family of primary malignant bone tumours and originate from bone as Osteosarcomas (OS), Chondrosarcomas (CS), Fibrosarcomas, Chordomas, ... Current conventional treatments for OS combine chemotherapy and surgery. Chemotherapy treatment is commonly given for OS over a period of 6-10 months, with a period of preoperative chemotherapy, to facilitate local surgical treatment. The conventional cocktail used in OS is composed by a minimum of three drugs (reference combination: methotrexate, doxorubicin and cisplatin (MAP)). The currently recommended treatments for Ewing sarcomas (for both localized and metastatic diseases) consist of multimodal approaches including surgery and/or radiotherapy associated to neoadjuvant and adjuvant chemotherapy, comprising respectively from 3 to 6, and then from 6 to 10 cycles. Doxorubicin, cyclophosphamide, ifosfamide, vincristine, dactinomycin and etoposide are considered as the most active substances. Current trials require combination chemotherapies, and most of them are based on the combination of 5-6 of these substances. Concerning chondrosarcomas, the treatment is adapted according to the subtype. Thus, the treatment regimen for mesenchymal chondrosarcomas and dedifferentiated chondrosarcomas differs. Indeed, an Ewing-type chemotherapy regimen is usually suggested to treat mesenchymal chondrosarcomas while dedifferentiated chondrosarcomas are often treated as high-grade bone sarcoma, with systemic and local therapies. Compared with surgery alone, multimodal treatment of high-grade sarcomas increases disease-free survival probabilities from only 10%-20% to 50-65% depending on the bone sarcoma type. In general, despite second-line treatment, the prognosis of recurrent disease has remained poor, with long-term post-relapse survival of <20%. The outcome of bone sarcoma has been dramatically improved by the addition of chemotherapy in the 70' and 80' but has remained remarkably stable in the last 3 decades, with a survival rate largely plateaued, despite introduction of novel regimens, both in localized and metastatic disease, in children and in adults. Primary bone cancer presented challenges in new drug development partly because of their rarity and heterogeneity. Thus, improving treatments for these diseases is a high priority, but advances have been few in recent years. In this context, maintenance therapy may be an interesting option as a way to prolong the benefit of first-line chemotherapy. Regorafenib may play a role in the maintenance setting for bone sarcomas (as improved Progression-Free Survival and sustained responses were observed in the REGOBONE study) in maintaining the initial response to standard treatments and delaying the need for further treatment at relapse, while exerting a manageable associated toxicity and minimal negative impact on health-related quality of life. Currently there is no available agent used as maintenance therapy after first-line treatments. In the context of a clinical trial with close monitoring, it is, thus, acceptable to consider a placebo-control group. On this basis, this study propose to conduct a double-blinded randomized controlled trial to evaluate the efficacy of regorafenib versus placebo in the treatment of patients with bone sarcomas, who have no evidence of disease after standard multimodal treatments based on the histological subtype. The main goal of the present study is then to explore whether sequential addition of regorafenib after completion of a standard treatment in patients with bone sarcomas would improve outcomes in term of event-free-survival (EFS) defined by local or distant recurrence of the disease. Results will be stratified on the "high-risk" versus "low-risk" of relapse. As response to neoadjuvant chemotherapy and metastatic status at time of diagnosis are known to be important on patient's outcome, stratification will rely on a combined criteria taking into account these two factors. Thus, "high-risk" of relapse will be defined by the group of patients who are poor responders to neoadjuvant chemotherapy and/or in metastatic setting at diagnosis, whereas "low-risk" of relapse will be defined by the group of patients who have no metastatic disease at time of diagnosis and are good responders to neoadjuvant chemotherapy. Fermer le détail

Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
CLCC INSTITUT CURIE		En recrutement IDF	04/09/2024 13:49:47	Contacter
CLCC INSTITUT GUSTAVE ROUSSY	Benjamin VERRET	En recrutement IDF	18/02/2024 16:59:05	Contacter
Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
AP-HP - Hôpital Cochin	Pascaline BOUDOU-ROUQUETTE	En recrutement IDF		Contact (sur clinicalTrials)
Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
Centre Oscar Lambret - 59020 - Lille - France	Cyril LERVAT	En recrutement		Contact (sur clinicalTrials)
Hôpital Jean Minjoz - 25000 - Besançon - France	Loïc CHAIGNEAU	En recrutement		Contact (sur clinicalTrials)
ICL Alexis Vautrin - 54519 - Vandœuvre-lès-Nancy - France	Maria RIOS	Recrutement non commencé		Contact (sur clinicalTrials)
ICO René Gauducheau - 44805 - Saint-Herblain - France	Emmanuelle BOMPAS	En recrutement		Contact (sur clinicalTrials)
Institut Bergonié - 33076 - Bordeaux - France	Antoine ITALIANO	En recrutement		Contact (sur clinicalTrials)
IUCT-Oncopole - 31059 - Toulouse - France	Thibaud VALENTIN	Recrutement non commencé		Contact (sur clinicalTrials)
Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
APHM - Hôpital Timone - 13385 - Marseille - France	Florence DUFFAUD	En recrutement		Contact (sur clinicalTrials)
Centre Hospitalier Régional de Strasbourg Hautepierre - 67098 - Strasbourg - France	Natacha ENTZ-WERLE	En recrutement		Contact (sur clinicalTrials)
Centre Hospitalier Universitaire de Poitiers - 86000 - Poitiers - France	Nicolas ISAMBERT	Recrutement non commencé		Contact (sur clinicalTrials)
Centre Hospitalier Universitaire de Saint-Etienne (CHUSE) - 42055 - Saint-Étienne - France	Claire BERGER	En recrutement		Contact (sur clinicalTrials)
Centre Léon Bérard - 69373 - Lyon - France	Jean-Yves BLAY	En recrutement		Contact (sur clinicalTrials)
ICM Val d'Aurelle - 34298 - Montpellier - France	Nelly FIRMIN	Recrutement non commencé		Contact (sur clinicalTrials)
Institut de Cancérologie Strasbourg Europe - 67033 - Strasbourg - France	Justine GANTZER	En recrutement		Contact (sur clinicalTrials)

Critères

Genre

Tous

Nombre d'inclusion

Critère d'inclusion

INCLUSION CRITERIA :

I1. Age ≥ 12 years at the day of consenting to the study;

I2. Patients must have histologically confirmed diagnosis of primary bone sarcoma
including but not limited to: Osteosarcomas, Ewing sarcomas, Chondrosarcomas,
Undifferentiated Pleomorphic Sarcomas (UPS), Leiomyosarcomas (LMS) and Angiosarcomas;

I3. Prior treatment for localized or metastatic disease for bone sarcoma must have been
completed, consisting of a standard multimodal treatment based on the histological
subtype:

For OS, (excepted head and neck localisations), neoadjuvant and/or adjuvant chemotherapy
should include methotrexate-based regimen for patients < 18 years old; patients ≥ 18
years old may have received either methotrexate-based regimen or anthracycline and
cisplatin-based regimen For head and neck OS, neoadjuvant and/or adjuvant chemotherapy
should include adriamycin, cisplatin or ifosfamide-based regimen.

For non-OS, neoadjuvant and/or adjuvant chemotherapy should include adriamycin and/or
cisplatin-based regimen.

I4. Recovery to 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);

I5. Interval between the last chemotherapy administration and the date of randomisation:
at least 4 weeks but no longer than 2 months;

I6. Confirmed complete remission or no evidence of disease (for metastatic disease);

Patients with pulmonary micro nodules can be included provided they do not meet the
following criteria:

- At least one lung nodule of 10mm or more

- And/or at least two nodules well limited between 6-9mm

- And/or at least 5 nodules well limited of 5mm or less All the other situations will
be considered as doubtful lesions except in case of metastatic disease confirmed
during the lung surgery of the residual lung lesions after pre-operative
chemotherapy. If no other metastatic localisation is detected at the initial
staging, the patient will be considered as localised disease and eligible for
randomisation.

I7. Life expectancy of greater than 12 months;

I8. Karnofsky Performance status ≥70 (patients younger than 18-year old) or ECOG
performance status < 2 (adult patients) ;

I9. Patients must have adequate bone marrow, renal, and hepatic function, as evidenced by
the following within 7 days of study treatment initiation:

- Absolute neutrophil count ≥ 1.5 Giga/l

- Platelets ≥ 100 Giga/l

- Haemoglobin≥ 9 g/dl

- Serum creatinine ≤ 1.5 x ULN

- Glomerular filtration rate (GFR) ≥30 ml/min/1.73m2 according to the Modified Diet in
Renal Disease (MDRD) abbreviated formula

- AST and ALT ≤2.5 x ULN ( ≤5.0 × ULN for patients with liver involvement of their
cancer)

- Bilirubin ≤1.5 X ULN

- 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 GGT
tests must be performed; hepatic isoenzymes 5-nucleotidase must be within the normal
range and/or GGT < 1.5 x ULN.

- Lipase ≤1.5 x ULN

- 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

I10. INR/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;

I11. Women of childbearing potential and male patients must agree to use adequate
contraception (Appendix 4) for the duration of treatment and for 7 months (210 days) in
WOCBP or 4 months (120 days) in men sexually active with WOCBP after the last dose of
regorafenib;

I12. Women of childbearing potential must have a negative serum β-HCG pregnancy test
within 7 days prior randomization and/or urine pregnancy test within 48 hours before the
first administration of the study treatment;

I13. 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;

I14. Patients must be willing and able to comply with scheduled visits, treatment plan,
laboratory tests and other study procedures;

I15. Patients covered by a medical insurance.

I16. Body Surface Area (BSA) ≥ 1.30m² at the time of consenting to the study.

NON-INCLUSION CRITERIA :

E1. Prior treatment with any VEGFR inhibitor (thus, any prior exposure to sunitinib,
sorafenib, pazopanib, bevacizumab, or other VEGFR inhibitor);

E2. All soft tissue sarcomas (including but not limited to soft tissue osteosarcomas and
Ewing soft tissue sarcomas) and chordomas;

E3. Prior history of other 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:

- 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;

E5. Uncontrolled hypertension (systolic blood pressure > 150mmHg or diastolic pressure >
90 mmHg despite optimal treatment);

E6. 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;

E7. Major surgical procedure, open biopsy or significant traumatic injury within 28 days
before the first study drug administration;

E8. Ongoing infection > Grade 2 according to NCI-CTCAE v5;

E9. Known history of human immunodeficiency virus (HIV) 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;

E10. Active hepatitis B or C 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;

E11. Dehydration according to NCI-CTC v5 Grade >1;

E12. 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);

E13. Patients with seizure disorder requiring medication;

E14. Concurrent enrolment in another clinical trial in which investigational therapies
are administered;

E15. Known hypersensitivity to the active substance or to any of the excipients;

E16. Pregnant women, women who are likely to become pregnant or are breast-feeding

E17. 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;

E18. Patients with history of non-compliance to medical regimens or unwilling or unable
to comply with the protocol;

E19. Interstitial lung disease with ongoing signs and symptoms at the time of informed
consent;

E20. Non-healing wound, non-healing ulcer, or non-healing bone fracture;

E21. Patients with evidence or history of any bleeding diathesis, irrespective of
severity;

E22. Any haemorrhage or bleeding event ≥ CTCAE v5 Grade 3 within 4 weeks prior to the
first study drug administration;

E23. 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;

E24. Patients using prohibited concomitant and/or concurrent medications (see section
"Prohibited concomitant/concurrent treatments);

E25.Patients under tutorship or curatorship.

Critère de non inclusion

NCT04055220 - A Randomized, Placebo-controlled, Double-blinded, Multicentre Study Evaluating the Efficacy and Safety of Regorafenib as Maintenance Therapy After First-line Treatment in Patients With Bone Sarcomas (REGOSTA)

Informations générales
Etablissements
Critères
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