MedulloblastomaPhase 1/2MEPENDAXNCT06485908
Axitinib and Oral Metronomic Etoposide for Pediatric Children and AYA Refractory/Relapsing Medulloblastoma and Ependymoma
A Phase 1/2 study testing administration of axitinib in combination with etoposide in people with Medulloblastoma and Ependymoma, run by Assistance Publique Hopitaux De Marseille.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 25 years
- Conditions the study is for
- Medulloblastoma, Ependymoma
- What is being tested?
- administration of axitinib in combination with etoposide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Oct 2024to Jan 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 43Show fewer
- 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.
Who cannot join
None listed.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Franceline CARTIER contact
About this study
Official title: MEPENDAX: Phase I/II Study of Axitinib (Inlyta®) and Oral Metronomic Etoposide for Pediatric Children and AYA Refractory/Relapsing Medulloblastoma and Ependymoma
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.
- Conditions
- Medulloblastoma, Ependymoma
- Being tested
- administration of axitinib in combination with etoposide
- Medical subject headings
- Medulloblastoma, Ependymoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
administration of axitinib in combination with etoposideDrug
- 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
- 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)
| Study group | Role | What they receive |
|---|---|---|
| Patients receiving axitinib in combination with etoposide | Experimental | 1. st stage: Dose escalation The first patient will be included at the level of 1.6 mg/m²/day of axitinib. Patients will be included by cohort of a maximum of 6 patients evaluable for DLT. In the absence of more than 2 patients with DLT during the first 28-day cycle, escalation to the next level will be allowed. Intra-patient dose escalation is not permitted. Non evaluable patients for DLT will be replaced. Six evaluable patients will be enrolled at the last dose level. RP2D will be the DMT or in the absence of DLT the maximum dose evaluated.
Treatment will be continued until progression, or unacceptable toxicity for a period of 1 year.
Depending on the number of DLTs observed, a maximum of 18 patients should be included.
2. nd stage: extension cohort For the second phase of the study, at RP2D, 2 cohorts of 9 patients (ependymoma, medulloblastoma) will be considered in the study. Treatment will be continued until progression, or unacceptable toxicity for a period of 1 year. Receives: Drug: administration of axitinib in combination with etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT)
During first stage
Measured: During the first 28 days (cycle 1)
Progression-free survival (PFS)
During second stage, progression-free survival (PFS) computed as the time interval from the beginning of treatment to the date of centrally-assessed with RAPNO criteria. A central review of all imaging is planned at the end of phase 1 and at the end of phase expansion to evaluate tumor response and progressions. PFS-duration of patients alive free of progression at last follow-up will be censored at the date of last visit.
Measured: 3 years (from start of treatment to last follow-up visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2024
- Study startOct 2024 (estimated)
- Primary completionApr 2026 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MedulloblastomaStudies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicolas ANDRE, Principal investigator, Assistance Publique - Hôpitaux de Marseille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06485908
- Sponsor's protocol ID
- RCAPHM23_0164
- Acronym
- MEPENDAX
- Status last verified
- Jun 2024
- First submitted
- 25 Jun 2024
- Last updated
- 3 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MEPENDAX: Phase I/II Study of Axitinib (Inlyta®) and Oral Metronomic Etoposide for Pediatric Children and AYA Refractory/Relapsing Medulloblastoma and Ependymoma
- ClinicalTrials.gov ID
- NCT06485908
- Acronym / sponsor ID
- MEPENDAX / RCAPHM23_0164
- Conditions
- Medulloblastoma, Ependymoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- Oct 2024 (estimated)
- Primary completion
- Apr 2026 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 3 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients receiving axitinib in combination with etoposide | Experimental | Drug: administration of axitinib in combination with etoposide1. st stage: Dose escalation The first patient will be included at the level of 1.6 mg/m²/day of axitinib. Patients will be included by cohort of a maximum of 6 patients evaluable for DLT. In the absence of more than 2 patients with DLT during the first 28-day cycle, escalation to the next level will be allowed. Intra-patient dose escalation is not permitted. Non evaluable patients for DLT will be replaced. Six evaluable patients will be enrolled at the last dose level. RP2D will be the DMT or in the absence of DLT the maximum dose evaluated. Treatment will be continued until progression, or unacceptable toxicity for a period of 1 year. Depending on the number of DLTs observed, a maximum of 18 patients should be included. 2. nd stage: extension cohort For the second phase of the study, at RP2D, 2 cohorts of 9 patients (ependymoma, medulloblastoma) will be considered in the study. Treatment will be continued until progression, or unacceptable toxicity for a period of 1 year. |
Who may qualify
- Ages
- 4 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (43 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| administration of axitinib in combination with etoposide1. 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) | Drug | Patients receiving axitinib in combination with etoposide |
Primary outcome
Dose-limiting toxicity (DLT)
Time frame: During the first 28 days (cycle 1)
During first stage
Progression-free survival (PFS)
Time frame: 3 years (from start of treatment to last follow-up visit)
During second stage, progression-free survival (PFS) computed as the time interval from the beginning of treatment to the date of centrally-assessed with RAPNO criteria. A central review of all imaging is planned at the end of phase 1 and at the end of phase expansion to evaluate tumor response and progressions. PFS-duration of patients alive free of progression at last follow-up will be censored at the date of last visit.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Franceline CARTIER contact
Nicolas ANDRE principal investigator
Assistance Publique - Hôpitaux de Marseille
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing administration of axitinib in combination with etoposide in people with Medulloblastoma and Ependymoma, run by Assistance Publique Hopitaux De Marseille.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 43 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nicolas ANDRE (0491386792, nicolas.andre@ap-hm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity (DLT) (time frame: During the first 28 days (cycle 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.