Phase Ib study of the combination of regorafenib with conventional chemotherapy for the treatment of newly diagnosed patients with multimetastatic Ewing sarcoma - REGO-INTER-EWING1
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 12
- 主要终点
- Dose-limiting toxicity (DLT) -DLT will be defined as any of the following haematological and non-haematological events (CTCAE v5.0) that occur during the DLT assessment period (4 weeks after the start of treatment = cycle 1) and are at least possibly related (possibly, probably, or definitely) attributable to VDC/IE + regorafenib
研究概览
简要总结
To determine the recommended Phase 2 dose (RP2D) of regorafenib in combination with standard backbone chemotherapy of VDC/IE in patients with newly diagnosed metastatic (other than lungs and/or pleura only) Ewing sarcoma.
入排标准
- 年龄范围
- 0 years 至 64 years（0-17 Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •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
- •Subject must be able to swallow and retain oral medication.
- •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.
- •Patients must be affiliated to a social security system or beneficiary of the same, as per local regulatory requirements (France only)
- •Metastatic disease
- •Age ≥2 years and <50 years (from second birthday to 49 years 364 days)
- •Patient assessed as medically fit to receive the Ewing sarcoma standard multimodal treatment and regorafenib, including: - Absolute Neutrophil Count (ANC) ≥ 0.75x109/L, platelets ≥ 75x109/L. - Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 5×ULN - Bilirubin ≤ 2×ULN - Creatinine < 2x ULN or creatinine clearance >60 ml/min/1.73 m2 - International normalized ratio (INR)/ Partial thromboplastin time (PTT) INR and PTT ≤ 1.5 x ULN INR & PTT ≤ 1.5xULN
- •Adequate cardiac function as evidenced by left ventricular ejection fraction (LVEF) ≥50%) at baseline, as determined by echocardiography
- •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
- •Patients >18 years old should have BP ≤ 150/90 mm Hg.
- •No prior treatment for Ewing sarcoma other than surgery
- •Negative pregnancy test for female patients of childbearing potential within 7 days prior to study registration
- •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
排除标准
- •Localized tumor or metastatic disease to lung/pleura only.
- •Follow-up not possible due to social, geographic or psychological reasons
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter absorption of oral drugs
- •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 mm Hg or diastolic pressure > 90 mm Hg on repeated measurement) despite optimal medical management
- •Previous arterial or venous thromboembolisms Grade ≥ 3 per CTCAE v5.0
- •Hypersensitivity to any active substance or to any excipients
- •Radiographic evidence of encasement or invasion of a major blood vessel or of intratumoral cavitation
- •Any anticoagulant therapy
- •Major surgical procedure or significant traumatic injury within 28 days before starting study treatment
- •Non-healing wound, ulcer or bone facture.
- •Uncontrolled systemic or local infection requiring systemic tratement
- •Interstitial lung disease with ongoing signs and symptoms.
- •Known prior history of HBV, HCV, HIV
- •Any other medical or other condition that, in the opinion of the investigator(s), would preclude the subject’s participation in this clinical study
- •Contra-indication to the Ewing sarcoma standard multimodal treatment
- •Pregnant or breastfeeding women or intending to become pregnant during the study.
结局指标
主要结局
Dose-limiting toxicity (DLT) -DLT will be defined as any of the following haematological and non-haematological events (CTCAE v5.0) that occur during the DLT assessment period (4 weeks after the start of treatment = cycle 1) and are at least possibly related (possibly, probably, or definitely) attributable to VDC/IE + regorafenib
Dose-limiting toxicity (DLT) -DLT will be defined as any of the following haematological and non-haematological events (CTCAE v5.0) that occur during the DLT assessment period (4 weeks after the start of treatment = cycle 1) and are at least possibly related (possibly, probably, or definitely) attributable to VDC/IE + regorafenib
Any grade ≥ 3 (hematological or non-hematological) toxicity leading to delay of start of day 15 by > 7 days (i.e: starting > day 21) or day 1 of cycle 2 by > 14 days ((i.e: starting > day 42)
Any grade ≥ 3 (hematological or non-hematological) toxicity leading to delay of start of day 15 by > 7 days (i.e: starting > day 21) or day 1 of cycle 2 by > 14 days ((i.e: starting > day 42)
Any dose interruption or reduction due to toxicity which results in administration of less than 80% of the planned dosage of regorafenib or 75% of the planned dosage of chemotherapy in the first cyle of 28 days of treatment.
Any dose interruption or reduction due to toxicity which results in administration of less than 80% of the planned dosage of regorafenib or 75% of the planned dosage of chemotherapy in the first cyle of 28 days of treatment.
Any grade ≥ 3 toxicity resulting in permanent discontinuation of the regorafenib
Any grade ≥ 3 toxicity resulting in permanent discontinuation of the regorafenib
Any grade 5 toxicity related to study treatment (death)
Any grade 5 toxicity related to study treatment (death)
次要结局
- Overall Survival (OS) and progression-free survival (PFS)
- Adverse events and toxicity, defined by CTCAE v5.0
- Histological response of the primary tumor to induction chemotherapy if surgery is performed as local control
- Radiological response of primary tumor, regional lymph nodes and/or metastases
研究者
Regulatory affairs officer
Scientific
Institut Gustave Roussy