Nimotuzumab in Combination With Radio-chemotherapy for the Treatment of Brainstem Tumor in Children

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of nimotuzumab in combination of radio-chemotherapy for the treatment of brainstem tumor in children.

Detailed Description
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Nimotuzumab (h-R3), a recombinant humanized monoclonal immunoglobulin G1 antibody that binds to the extracellular domain of EGFR, which blocks the binding of EGF and transforming growth factor-α to EGFR. High expression of EGFR protein in glioma has been associated with tumor progression and enhanced tumorigenicity. Several clinical trials have demonstrated the anti-tumor effects of nimotuzumab, such as head and neck cancer and esophageal cancer15. The purpose of this study was to evaluate the efficacy of nimotuzumab in combination of radio-chemotherapy for the treatment of brainstem tumors in children.

Official Title
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Phase 2 Study of Nimotuzumab in Combination With Radio-chemotherapy for the Treatment of Brainstem Tumor in Children

Conditions
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Childhood Brain Stem Neoplasm

Intervention / Treatment
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* Drug: Nimotuzumab
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be >/= 3 and </= 21 years of age. Patients must have a newly diagnosed or progressive brain stem tumor. If biopsy has been performed, patients with both high and low grade astrocytomas are eligible. Non-histologically confirmed brain stem tumors are eligible. Neuroradiographic confirmation of brain stem glioma is mandatory for study entry. Cervicomedullary junction tumors are ineligible. Patients with a diagnosis of NF-1 are ineligible. Patients must be registered within 6 weeks from diagnosis or recurrence. Patients must have life expectancy > 6 weeks. Patients must have adequate hematologic and renal function: ANC >1,000/ul, platelets>100,000/ul and creatinine normal for age: </= 0.7 mg/dl (age 3-10yrs.), </= 1.0 mg/dl (11-12yrs.). and </= 1.2 (13-21yrs.). Written informed consent must be obtained according to institutional guidelines. Exclusion Criteria: Cervicomedullary junction tumors are ineligible. Patients with a diagnosis of NF-1 are ineligible. Pregnant or nursing women are ineligible. Patients must not start treatment until informed consent is given and the patient is registered.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 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: radio-chemotherapy plus nimotuzumab<br>Radiotherapy: The total radiation dose is 52.2Gy (1.8Gy fractions). Chemotherapy: Nimotuzumab, given during radiotherapy, is administered via intravenous drip with a dosage of 150mg/m2, weekly, for 6 consecutive weeks. After radiotherapy and evaluation, disease progression-free patients will continue to receive Nimotuzumab treatment biweekly until disease relapse or progression. Temozolomide is applied to these patients as a chemotherapy drug with a dosage of 75mg/m2, daily. The chemotherapy and radiation therapy are combined as temozolomide is taken 1 hour prior to every fraction of radiotherapy. In 4 weeks after the completion of radiotherapy, temozolomide is given for 8 cycles. | Drug: Nimotuzumab<br>* Nimotuzumab given during radiotherapy, is administered via intravenous drip with a dosage of 150mg/m2, weekly, for 6 consecutive weeks. After radiotherapy and evaluation, disease progression-free patients will continue to receive Nimotuzumab treatment biweekly until disease relapse or progression.<br>* Other names: h-R3, BIOMAb EGFR, Biocon;Drug: Temozolomide<br>* Temozolomide is applied to these patients as a chemotherapy drug with a dosage of 75mg/m2, daily. The chemotherapy and radiation are combined as temozolomide is taken 1 hour prior to every fraction of radiotherapy. In 4 weeks after the completion of radiotherapy, temozolomide is given for 8 cycles (dosage: the 1st cycle, 150mg/m2, daily × 5 days, 4 weeks a cycle; the 2-8th cycle, 200mg/m2, daily × 5 days, 4 weeks a cycle and repeated again).<br>* Other names: brand names Temodar and Temodal and Temcad;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |  | first analysis will occur 1 month after accrual of all patients | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival(PFS) |  | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Overall survival (OS) |  | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 
| Objective response rate (ORR) |  | first analysis will occur 1 month after accrual of all patients | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiation Therapy, Brainstem Tumor in Children