Status:

NOT_YET_RECRUITING

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

Lead Sponsor:

Assistance Publique Hopitaux De Marseille

Conditions:

Medulloblastoma

Ependymoma

Eligibility:

All Genders

4-25 years

Phase:

PHASE1

PHASE2

Brief 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 ...

Eligibility Criteria

Inclusion

  • 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.

Exclusion

    Key Trial Info

    Start Date :

    October 1 2024

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ESTIMATED

    End Date :

    January 1 2030

    Estimated Enrollment :

    40 Patients enrolled

    Trial Details

    Trial ID

    NCT06485908

    Start Date

    October 1 2024

    End Date

    January 1 2030

    Last Update

    July 3 2024

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