Bevacizumab and Nimustine in Patients With Recurrent High Grade Glioma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether bevacizumab and nimustine are effective in the treatment of recurrent high grade glioma and to explore whether there is any subgroup being sensitive to this therapeutic protocol.

Detailed Description
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Although anti-angiogenesis therapy for glioblastoma(GBM) are showing promise, GBMs often develop resistance to treatment within months or weeks after salvage therapy. There are still no effective markers to predict the response rate to bevacizumab. So the investigators initiate a single-arm Phase II study to evaluate the efficacy and tolerability of bevacizumab and nimustine regimen and to explore the predictive markers in patients with recurrent high-grade glioma.

Official Title
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Phase II Study of Bevacizumab and Nimustine in Patients With Recurrent High Grade Glioma

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Nimustine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological diagnosis of primary tumor as high-grade gliomas (WHO III or IV) All patients should complete radiotherapy and chemotherapy for primary gliomas Enhanced MRI and magnetic resonance spectroscopy showed unequivocal evidence of tumor recurrence or progression. Those patients underwent surgical resection after tumor recurrence can also be enrolled if histological diagnosis of GBM is available, and MRI within 3 days after operation is needed. The patients with recurrent gliomas didn't undergo bevacizumab therapy before enrollment. The time to be enrolled should be more than 90 days after the radiation therapy, more than 28 days after operation for recurrent tumor or prior chemotherapy. Eastern Cooperative Oncology Group score: 0-2 Written informed consent Laboratory test: Neutrophil count > 1.5*10^9/L, platelet count > 100*109/L, hemoglobin > 8 g/dL, blood urea nitrogen and creatinine < 1.5 upper limit of normal(ULN), blood total bilirubin and conjugated bilirubin < 1.5 ULN, alanine aminotransferase(ALT) and aspartate aminotransferase(AST) < 3 ULN, alkaline phosphatase(AKP) < 2 ULN Exclusion Criteria: Pregnant or lactating women Allergic to administered drugs Radiation therapy in the previous 90 days before enrollment The patients with recurrent gliomas were treated with bevacizumab therapy before enrollment. Acute infection in need of antibiotics intravenously Participation in other clinical trials in the 90 days before enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment<br>Patients are treated with bevacizumab and nimustine. Every 6 weeks is defined as one therapeutic cycle. Adverse effect is evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE; version 4.03). Hematologic toxicity is evaluated every 2 weeks. Liver function, renal function, and electrolytes are assessed every 4-6 weeks. Platelet should be no less than 100*10^9/L and neutrophil count should be no less than 1.5*10^9/L. | Drug: Bevacizumab<br>* Bevacizumab is administered intravenously at 5mg/kg every 3 weeks.<br>* Other names: Avastin;Drug: Nimustine<br>* Nimustine is administered intravenously at 90mg/m^2 to 110mg/m^2 every 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause response to treatment | Response will be evaluated according to the Response Assessment in Neuro-Oncology(RANO) criteria.Imaging Data (postcontrast T1W,T2/FLAIR),clinical symptoms and corticosteroid use will be collected in each participant and response assessment will be performed by one neurosurgeon and one neuroradiologist. | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality |  | One year | 
| All cause disease progression | Progression disease will be evaluated according to the RANO criteria | 3 weeks | 
| All cause severe toxicities | All toxicities will be assessed and graded according to CTCAE v4.03 | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bevacizumab, Nimustine, Pathology, Molecular