Informations générales (source: ClinicalTrials.gov)
Phase Ib Study of the Combination of Regorafenib With Conventional Chemotherapy for the Treatment of Newly Diagnosed Patients With Multimetastatic Ewing Sarcoma (REGO-INTER-EWI)
Interventional
Phase 1
Gustave Roussy, Cancer Campus, Grand Paris (Voir sur ClinicalTrials)
juin 2023
juin 2026
03 décembre 2024
New drug efficacy in ES has been disappointing in the last decades and no new drugs have
been successfully introduced up to now in front line treatment. Among the tested drugs,
early clinical data suggest that strategies using multi-targeted tyrosine kinase
inhibitors (TKI) with anti-angiogenic activities are among the most efficient and may be
beneficial in the treatment of patients with ES.
Several TKI have been and are currently being tested as single-agent in patients with
relapsed/refractory ES with encouraging results in phase II trials. Regorafenib has shown
promising activity in Ewing sarcoma relapse setting, Nevertheless, regorafenib has never
been combined with the intensive chemotherapy VDC/IE schedule and therefore this
combination needs to be evaluated in order to avoid dose reduction of the current
standard treatment and hence its efficacy.
The current clinical trial has been therefore designed to test the feasibility of
regorafenib with ES conventional chemotherapy. It consists of a phase Ib that will only
recruit patients with multi-metastatic (other than lungs/pleura only) ES, that present
the highest unmet medical need (2 year EFS: 33%, similar to patients with
relapse/refractory ES).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/12/2024 12:44:14 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Pablo BERLANGA | 14/06/2024 07:17:34 | Contacter | ||
Critères
Tous
Inclusion Criteria:
1. Any histologically and genetically confirmed Ewing sarcoma of bone or soft tissue,
or round cell sarcomas which are 'Ewing's-like' but negative for EWSR1 gene
rearrangement
2. Metastatic disease
3. Age ≥2 years and <50 years (from second birthday to 49 years 364 days)
4. Patient assessed as medically fit to receive the Ewing sarcoma standard multimodal
treatment and regorafenib, including:
- Absolute Neutrophil Count (ANC) ≥ 0.75x10^9/L, platelets ≥ 75x10^9/L.
- Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 5×ULN
- Bilirubin ≤ 2×ULN
- Creatinine < 2x ULN or creatinine clearance >60 ml/min/1.73 m^2
- International normalized ratio (INR)/ Partial thromboplastin time (PTT). INR
and PTT ≤ 1.5 x ULN. INR & PTT ≤ 1.5xULN
5. Adequate cardiac function as evidenced by left ventricular ejection fraction (LVEF)
≥50%) at baseline, as determined by echocardiography
6. Adequately controlled blood pressure (BP) with or without antihypertensive
medications, defined as: a BP <95th percentile for sex, age, and height at screening
(as per National Heart Lung and Blood Institute [NHLBI] guidelines) and no change in
antihypertensive medications within 1 week prior to Cycle 1 Day 1. Patients >18
years old should have BP ≤ 150/90 mmHg.
7. No prior treatment for Ewing sarcoma other than surgery
8. Negative pregnancy test for female patients of childbearing potential within 7 days
prior to study registration.
9. Patient agrees to use highly effective contraception during therapy and for 12
months after last trial treatment (females) or 6 months after last trial treatment
(males), where applicable
10. Subject must be able to swallow and retain oral medication.
11. Written informed consent from the patient and/or the parent/legal guardian,
according to local, regional or national regulation prior to any study specific
procedures.
12. Patients must be affiliated to a social security system or beneficiary of the same,
as per local regulatory requirements (France only)
1. Any histologically and genetically confirmed Ewing sarcoma of bone or soft tissue,
or round cell sarcomas which are 'Ewing's-like' but negative for EWSR1 gene
rearrangement
2. Metastatic disease
3. Age ≥2 years and <50 years (from second birthday to 49 years 364 days)
4. Patient assessed as medically fit to receive the Ewing sarcoma standard multimodal
treatment and regorafenib, including:
- Absolute Neutrophil Count (ANC) ≥ 0.75x10^9/L, platelets ≥ 75x10^9/L.
- Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 5×ULN
- Bilirubin ≤ 2×ULN
- Creatinine < 2x ULN or creatinine clearance >60 ml/min/1.73 m^2
- International normalized ratio (INR)/ Partial thromboplastin time (PTT). INR
and PTT ≤ 1.5 x ULN. INR & PTT ≤ 1.5xULN
5. Adequate cardiac function as evidenced by left ventricular ejection fraction (LVEF)
≥50%) at baseline, as determined by echocardiography
6. Adequately controlled blood pressure (BP) with or without antihypertensive
medications, defined as: a BP <95th percentile for sex, age, and height at screening
(as per National Heart Lung and Blood Institute [NHLBI] guidelines) and no change in
antihypertensive medications within 1 week prior to Cycle 1 Day 1. Patients >18
years old should have BP ≤ 150/90 mmHg.
7. No prior treatment for Ewing sarcoma other than surgery
8. Negative pregnancy test for female patients of childbearing potential within 7 days
prior to study registration.
9. Patient agrees to use highly effective contraception during therapy and for 12
months after last trial treatment (females) or 6 months after last trial treatment
(males), where applicable
10. Subject must be able to swallow and retain oral medication.
11. Written informed consent from the patient and/or the parent/legal guardian,
according to local, regional or national regulation prior to any study specific
procedures.
12. Patients must be affiliated to a social security system or beneficiary of the same,
as per local regulatory requirements (France only)
1. Localized tumor or metastatic disease to lung/pleura only.
2. Contra-indication to the Ewing sarcoma standard multimodal treatment
3. Pregnant or breastfeeding women or intending to become pregnant during the study.
4. Follow-up not possible due to social, geographic or psychological reasons
5. Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter absorption of oral drugs
6. A clinically significant ECG abnormality, including a marked prolonged QTcF interval
(eg, a repeated demonstration of a QTcF interval >480 msec) Clinically significant,
uncontrolled heart disease (including history of any cardiac arrhythmias, e.g.,
ventricular, supraventricular, nodal arrhythmias, or conduction abnormality,
unstable angina, active coronary artery disease and myocardial infarction within 6
months before randomization.) Uncontrolled hypertension (systolic pressure >150 mmHg
or diastolic pressure > 90 mmHg on repeated measurement) despite optimal medical
management
7. Previous arterial or venous thromboembolisms Grade ≥ 3 per CTCAE v5.0
8. Hypersensitivity to any active substance or to any excipients
9. Radiographic evidence of encasement or invasion of a major blood vessel or of
intratumoral cavitation
10. Major surgical procedure or significant traumatic injury within 28 days before
starting study treatment
11. Non-healing wound, ulcer or bone fracture.
12. Uncontrolled systemic or local infection requiring systemic treatment
13. Any anticoagulant therapy (risk of hemorrhage with Regorafenib)
14. Interstitial lung disease with ongoing signs and symptoms.