Nimotuzumab in Combined With Chemoradiotherapy to Treat the Newly Diagnosed Diffuse Intrinsic Pontine Glioma in Children

Study Overview
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Brief Summary
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This is a prospective, open-label, single arm, multicenter clinical study. The purpose of the study is to evaluate the clinical efficacy and safety of combination Nimotuzumab with concurrent radiochemotherapy in children with newly diagnosed diffuse intrinsic pontine glioma(DIPG).

Detailed Description
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This clinical study is designed as a prospective, open-label, single arm, multicenter study to evaluate the clinical efficacy and safety of combination Nimotuzumab with concurrent radiochemotherapy in children with newly diagnosed diffuse intrinsic pontine glioma(DIPG). The main endpoint is objective response rate, 1-year overall survival rate is also observed.

Official Title
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A Multicenter, Prospective, Open and Single Arm Clinical Study of Nimotuzumab Combined With Concurrent Radiochemotherapy in the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) in Children

Conditions
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Diffuse Intrinsic Pontine Glioma

Intervention / Treatment
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* Drug: Nimotuzumab+CRT(concurrent IMRT and TMZ)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary and sign a consent form; Age 3-15 years old, gender unlimited; Histology or imaging diagnosed as diffuse intrinsic pontine glioma, patients haven't received any anti-tumor treatment; According to the RANO criteria, at least one measurable lesion; Before enrollment, the results of laboratory examination are in accordance with: Blood routine test: platelet count ≥ 100 × 10^9/L; absolute neutrophil count ≥ 1.5 × 10^9/L or leukocyte count ≥ 3.0 × 10^9/L; hemoglobin ≥ 90g/L; Blood biochemistry: aspartate aminotransferase#AST# ≤ 3 ×Upper Limit Of Normal#ULN#; alanine aminotransferase#ALT# ≤ 3 × ULN; total bilirubin ≤ 1.5 × ULN; serum creatinine ≤ 1.5 × ULN; Lansky score ≥ 60; Expected survival time ≥ 3 months; Fertile subjects are willing to take contraceptive measures during the study period. Exclusion Criteria: Recurrent DIPG; Have received any other anti-tumor treatment for DIPG, including surgical treatment (except biopsy), chemotherapy, radiotherapy, targeted drugs, immunotherapy, etc; Uncontrollable infection, epilepsy and / or hypertension and / or hyperglycemia; Human immunodeficiency virus #HIV# infection or active hepatitis B infection or hepatitis C infection; Active hemorrhage found by CT or MRI before inclusion and / or inability to carry out CT and MRI examination; Major operation (except biopsy) were performed within four weeks before inclusion; Decompensated heart failure (NYHA grades III and IV), unstable angina, acute myocardial infarction, persistent and clinically significant arrhythmia within three months of inclusion; Have other malignant tumor history; Known allergy to Nimotuzumab, temozolomide or its analogues or any component of the prescription; Unable to tolerate radiotherapy; Other reasons that are not suitable to participate in this study according to the researcher's judgment.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 15 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: Experimental<br>Nimotuzumab+CRT(concurrent IMRT and TMZ) | Drug: Nimotuzumab+CRT(concurrent IMRT and TMZ)<br>* Drug: Nimotuzumab Concurrent radiochemotherapy period, 150mg/m2, weekly, for 6 weeks; Maintenance period, from the 7th to the 52nd week, 150mg/m2, every two weeks until disease progression or intolerable toxicity. Other Names: h-R3 Drug: Temozolomide Concurrent radiochemotherapy period, 75mg/m2, daily, for 6 weeks; Maintenance period, rest from the 7th to 10th weeks, from the 11th week, 150-200mg/m2, day1 to day5, 21 days for a cycle, for 6 cycles. Other Names: TMZ<br>* Other names: h-R3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate #ORR# assessed by the Independent Review Committee | Proportion of patients with partial or complete response in tumor burden as defined by RECIST. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year overall survival | The possibility that a patient who has lived for 1 year after treatment will still survive. OS is defined as the time from enrollment to death. | Up to 12 months | 
| Progression-free survival#PFS# | PFS is defined as the time from enrollment to disease progression or death from any cause. | Up to 12 months | 
| Incidence of adverse events | An adverse event is any adverse event that occurs in a patient or subject of a drug clinical study. | Up to 30 days after last administration of Nimotuzumab | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nimotuzumab, Temozolomide, DIPG