Axitinib and Oral Metronomic Etoposide for Pediatric Children and AYA Refractory/Relapsing Medulloblastoma and Ependymoma

Trial Title: Axitinib and Oral Metronomic Etoposide for Pediatric Children and AYA Refractory/Relapsing Medulloblastoma and Ependymoma

NCT ID: NCT06485908

Condition: Medulloblastoma
Ependymoma

Conditions: Official terms:
Ependymoma
Medulloblastoma
Etoposide
Axitinib

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: administration of axitinib in combination with etoposide
Description: 1. st stage: - Axitinib (Inlyta®) PO, in the morning and in the evening every day - Level -1 : Dose 1.2 mg/m² - Level 1: Dose 1.6 mg/m² - Level 2: Dose 2.0 mg/m² - Level 3: Dose 2.4 mg /m² (equivalent to 4 mg in adults) - Etoposide (50 mg capsules or in the form of etoposide phosphate if required): 25 mg/m²/day in the evening orally every day fasting (capped to a maximum of 50 mg/day) First patient will be enrolled at dose level 1 2. nd stage: - Axitinib (Inlyta®) dosing as selected at the 1st stage - Etoposide (50 mg capsules or in the form of etoposide phosphate if required): 25 mg/m2/ day in the evening orally every day fasting(capped to a maximum of 50 mg/day)
Arm group label: Patients receiving axitinib in combination with etoposide

Summary: It is an open multicentric phase I/II trial with axitinib (Inlyta®) and metronomic delivery of etoposide for children, adolescent and young adults (AYA) with refractory/ relapsing solid tumors. It is a two-stage trial: First stage: To determine the Maximum Tolerated Dose (MTD) of the combination of axitinib and oral metronomic etoposide for patient with medulloblastoma or ependymoma Second stage: Extension cohort evaluating the preliminary efficacy at the recommended dose for the phase II (RDP2) of the combination. The 2nd stage will start after a meeting of independent data monitoring committee (IDMC). Two cohorts of 9 patients with ependymoma and medulloblastoma Patients treated at first stage won't be included in the second stage.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Histologically proven diagnosis of ependymoma or medulloblastoma - 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 - 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. Non-inclusion Criteria - 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. Evidence of > Grade 1 recent CNS hemorrhage on the baseline MRI or 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. - Presence of any NCI-CTCAE v5 grade ≥ 2 treatment-related extra-hematological toxicity with the exception of alopecia, ototoxicity or peripheral neuropathy. - Known congenital immunodeficiency. - 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. - Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery, but for these procedures, a 48 hour interval must be maintained before the first dose of the investigational drug is administered. - Bleeding disorder. - 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 hypersensitivity to any study drug or component of the formulation. - Absence of effective contraception in patients of childbearing age (see appendix 3) - Pregnant or nursing (lactating) females. - Patients with galactose intolerance, lactase deficiency or glucose or galactose malabsorption syndrome (rare hereditary diseases). - Severe infections requiring parenteral antibiotic therapy. - Inability to undergo medical monitoring of the trial for geographic, social or psychological reasons.

Gender: All

Minimum age: 4 Years

Maximum age: 25 Years

Healthy volunteers: No

Start date: October 2024

Completion date: January 2030

Lead sponsor:
Agency: Assistance Publique Hopitaux De Marseille
Agency class: Other

Source: Assistance Publique Hopitaux De Marseille

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06485908