2023-509585-38-00招募中2 期
MEPENDAX: Phase I/II study of axitinib (Inlyta®) and oral metronomic etoposide for pediatric children and AYA with refractory/relapsing medulloblastoma and ependymoma
适应症
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 7
- 主要终点
- First stage: The Dose-Limiting Toxicity (DLT) will be assessed over the first 28-day cycles, according to the NCI CTCAE V5
研究概览
简要总结
First stage (Escalation part): to determine the MTD of axitinib when combined to a fixed dose of oral metronomic etoposide Second stage (Extension part): to estimate the efficacy of axitinib when used at the dose determined during the escalating part of the study, in combination with the fixed dose of oral metronomic etoposide in terms of progression-free survival (PFS), in children and AYA with refractory / relapsing medulloblastoma or ependymoma.
研究设计
- 分配方式
- Non-randomized
- 主要目的
- Stage 2
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 64 years（18-64 Years, 0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •Histologically proven diagnosis of ependymoma or medulloblastoma.
- •Able to take oral treatments
- •Adequate organ function: Hematologic criteria: - Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 (unsupported) - Platelet count ≥ 100,000/mm3 (unsupported) - Hemoglobin ≥ 8.0 g/dL (transfusion is allowed) Cardiac function : - Shortening fraction (SF) >29% and left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography (mandatory only for patients who have received cardiotoxic therapy). Renal and hepatic function: - Serum creatinine < 1.5 x upper limit of normal (ULN) for age - Total bilirubin < 1.5 x ULN - Alanine aminotransferase (ALT)/ Aspartate aminotransferase (AST)/ < 2.5 x ULN
- •Able to comply with scheduled follow-up and with management of toxicity.
- •Females of child bearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment.
- •Sexually active patients must agree to use adequate and appropriate contraception (in accordance with Clinical Trials Facilitation and Coordination Group (CTFG) recommendations) while on study drug and for 6 months after stopping the study drug.
- •Patient able to comfortably swallow capsules.
- •Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted according to local, regional or national guidelines.
- •Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
- •Methyloma classification performed or available material for methyloma analysis
- •Confirmed progressive or refractory disease despite standard therapy, or for which no effective standard therapy exists
- •Male and female subjects with > 4 to ≤ 25 years of age at inclusion
- •Weight > 20 kg
- •Evaluable target lesion(s) according to RAPNO
- •Performance status: Karnofsky performance status (for patients >12 years of age) or Lansky Play score (for patients ≤12 years of age) ≥ 70%. Patients who are unable to walk because of paralysis or stable neurological disability, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- •Life expectancy ≥ 3 months
- •No known allergy to any of the compounds in the experimental treatment
排除标准
- •Chemotherapy within 21 days of day 1 from the start of study treatment. This period can be shortened in the case of treatment with vincristine (2 weeks) and extended to 6 weeks in the case of treatment with nitrosureas. The period is set to 5 half-lives in the case of targeted therapies or metronomic chemotherapy. The period is set to 2 weeks after bevacizumab administration.
- •Bleeding disorder
- •Inability to undergo medical monitoring of the trial for geographic, social or psychological reasons Known hypersensitivity to any study drug or component of the formulation.
- •Hypersensitivity to any study drug or component of the formulation.
- •Absence of effective contraception in patients of childbearing age
- •Pregnant or nursing (lactating) females.
- •Evidence of > Grade 1 recent CNS hemorrhage on the baseline MRI scan
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
- •Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening)
- •Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.
- •Known congenital immune-deficiency
- •Presence of any NCI-CTCAE v5 grade ≥ 2 treatment-related extra-hematological toxicity with the exception of alopecia, ototoxicity or peripheral neuropathy.
- •Radiotherapy within the 2 months preceding D1 of the start of study treatment. Palliative RT on a non-target lesion is allowed up to 1 weeks before beginning of treatment.
- •Invasive procedure/surgery during the last 15 days.
结局指标
主要结局
First stage: The Dose-Limiting Toxicity (DLT) will be assessed over the first 28-day cycles, according to the NCI CTCAE V5
First stage: The Dose-Limiting Toxicity (DLT) will be assessed over the first 28-day cycles, according to the NCI CTCAE V5
Second stage: Progression-free survival (PFS) computed as the time interval from the date of beginning of treatment to the date of centrally-assessed progression or death from any cause. The progression will be based on the RAPNO criteria. A central review of all imaging will evaluate tumor response and progressions at end of dose escalation phase and at end of expansion phase. PFS will be censored at the date of last visit.
Second stage: Progression-free survival (PFS) computed as the time interval from the date of beginning of treatment to the date of centrally-assessed progression or death from any cause. The progression will be based on the RAPNO criteria. A central review of all imaging will evaluate tumor response and progressions at end of dose escalation phase and at end of expansion phase. PFS will be censored at the date of last visit.
次要结局
- Adverse events (type, grade) graded according to the NCI CTCAE V5, per 28-day cycle and over the whole treatment duration. All AE occurring during treatment or in the 28 days after end of treatment will be reported, regardless of reported causal relationship, except symptoms related to the underlying disease or disease progression.
- Tumor response during treatment, centrally assessed using RAPNO criteria. The best overall response will be defined as the best response recorded from beginning of treatment until disease progression
- Overall survival, computed as the time interval from the date of beginning of treatment to the date of death from any cause. Survival of patients alive at last follow-up will be censored at the date of last visit.
- Relative dose-intensity of the different drugs, estimated for each drug as the ratio between the computed dose-intensity (cumulative dose expressed in mg/m² divided by the study duration and expressed in mg/m²/week) and the protocol dose-intensity.
- First stage: Calculate PK parameters of oral axitinib combined with etoposide
- Ancillary study: exploration of molecular signature in blood or CSF - Progression-free survival, defined as the time from randomization to recurrence, development of second primary cancer, or death from any cause. Overall survival defined as the time from randomization to death from any cause.
研究者
Professor Nicolas ANDRE
Scientific
Assistance Publique Hopitaux De Marseille
研究点 (7)
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