Combination of Irinotecan and Temozolomide in Children With Brain Tumors.

Study Overview
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Brief Summary
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This study will assess the rate of objective confirmed tumor response of irinotecan in combination with temozolomide in children with recurrent or refractory medulloblastoma and in children with newly diagnosed high-grade glioma.

Official Title
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Phase 2 Single-Arm, Open Label Study Of Irinotecan In Combination With Temozolomide In Children With Recurrent Or Refractory Medulloblastoma And In Children With Newly Diagnosed High-Grade Glioma.

Conditions
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Glioma, Medulloblastoma

Intervention / Treatment
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* Drug: Irinotecan
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort 1: Recurrent or refractory medulloblastoma in which current standard treatment approaches have failed; biopsy is not required for recurrent disease. Cohort 2: Newly-diagnosed high-grade glioma (World Health Organization [WHO] grade 3 or 4) Life expectancy ≥ 3 months Exclusion Criteria: Diagnosis of brainstem glioma Concurrent administration of any other anti-tumor therapy Pre-existing uncontrolled diarrhea

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temozolomide + Irinotecan<br> | Drug: Irinotecan<br>* Irinotecan 10 mg/m^2 per day on days 1-5 and days 8-12 in repeated 3 week cycles<br>Drug: Temozolomide<br>* Temozolomide 100-125 mg/m^2 daily on days 1-5 in repeated 3 week cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response of Complete Response or Partial Response | Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR). CR persisted on repeat imaging study at least (≥) 4 weeks after initial documentation of response. PR, for bidimensionally measurable disease, was a decrease by ≥50% of the sum of the products of the largest perpendicular diameters of all measurable lesions as determined by 2 observations not less than 4 weeks apart. Best overall response recorded any time while the participant was receiving treatment. External Response Review Committee (ERRC) assessment. | Baseline to 1 Year (medulloblastoma), Baseline to 6 Weeks (high-grade glioma) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response of Complete Response or Partial Response, Investigator's Assessment | Percentage of participants with objective response based assessment of confirmed CR or confirmed PR. CR persisted on repeat imaging study ≥4 weeks after initial documentation of response. PR, in case of bidimensionally measurable disease, was a decrease by ≥50% of the sum of the products of the largest perpendicular diameters of all measurable lesions as determined by 2 observations not less than 4 weeks apart. Best overall response could be recorded any time while the participant was receiving treatment. Investigator's assessment. | Baseline to 1 Year (medulloblastoma), Baseline to 6 Weeks (high-grade glioma) | 
| Duration of Response | Median duration (50%) of tumor response for participants with objective disease response: who have not progressed or died due to any cause; with a response and subsequent progression or death due to any cause for duration of response (DR). DR was defined as time from start of first documented objective tumor response (CR or PR) to first documented objective tumor progression or death due to any cause, whichever occurred first. DR (calculated in Weeks) = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7. Investigator's assessment. | Baseline to Date of Tumor Response (Up to 1 Year) | 
| Time to Treatment Failure (TTF) | TTF was defined as the time from the date of first dose of study treatment to the date of the first documentation of progressive disease (PD), the date of treatment discontinuation except completion of treatment, or date of death due to cancer. Investigator's assessment. | Baseline to Date of Treatment Failure (Up to 1 Year) | 
| Time to Tumor Progression (TTP) | TTP was defined as the time in months from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever came first. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7 multiplied by 4.33. Tumor progression was determined from oncologic assessment data (where data met the criteria for PD). Investigator's assessment. | Baseline to Date of Progression (Up to 1 Year) | 
| Overall Survival (OS) | Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7 multiplied by 4.33. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). Investigator's assessment. | Baseline to Date of Death (Up to 1 Year After Treatment) |