Informations générales (source: ClinicalTrials.gov)
A Multicentre Phase II Study of Efficacy of Regorafenib as Maintenance Treatment in Patients With High Grade Bone Sarcomas at Diagnosis or Relapse and Without Complete Remission After Standard Treatment (REGOMAIN)
Interventional
Phase 2
Centre Leon Berard (Voir sur ClinicalTrials)
juillet 2021
juillet 2026
24 septembre 2024
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/09/2024 13:49:40 | Contacter | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Nathalie GASPAR | 11/04/2024 10:50:58 | 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 | 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 | |||||
| Centre Georges Francois Leclerc - 21079 - Dijon - France | Alice HERVIEUX | Contact (sur clinicalTrials) | |||
| Centre Leon Berard - 69373 - Lyon - France | Mehdi BRAHMI | Contact (sur clinicalTrials) | |||
| Centre Oscar Lambret - 59020 - Lille - France | Nicolas PENEL | Contact (sur clinicalTrials) | |||
| CHRU Hôpital Hautepierre - 67098 - Strasbourg - France | Natacha ENTZ WERLE | Contact (sur clinicalTrials) | |||
| Chu Besancon - 25030 - Besançon - France | Loïc CHAIGNEAU | Contact (sur clinicalTrials) | |||
| Chu Saint-Etienne - 42270 - Saint-Priest-en-Jarez - France | Claire BERGER | Contact (sur clinicalTrials) | |||
| Hopital de La Timone - 13385 - Marseille - France | Contact (sur clinicalTrials) | ||||
| Hotel Dieu Nantes - 44093 - Nantes - France | Morgane CLEIREC | Contact (sur clinicalTrials) | |||
| ICANS - 67200 - Strasbourg - France | Justine GANTZER | Contact (sur clinicalTrials) | |||
| Icm Val D'Aurelle - 34298 - Montpellier - France | Nelly FIRMIN | Contact (sur clinicalTrials) | |||
| Ico Rene Gauducheau - 44805 - Saint-Herblain - France | Emmanuelle BOMPAS | Contact (sur clinicalTrials) | |||
| Institut Bergonie - 33076 - Bordeaux - France | Maud TOULMONDE | Contact (sur clinicalTrials) | |||
| Iuct Oncopole - 31059 - Toulouse - France | Thibaud VALENTIN | Contact (sur clinicalTrials) | |||
Critères
Tous
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
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
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.