Bevacizumab and Nimustine in Patients With Recurrent High Grade Glioma

Phase 2

Completed

• Conditions: Glioblastoma
• Interventions: Drug: Bevacizumab; Drug: Nimustine

• Registration Number: NCT02698280
• Lead Sponsor: Huashan Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2016-02-20
• Study First Submitted QC: 2016-02-28
• Study First Posted: 2016-03-03
• Primary Completion: 2018-01
• Study Completion: 2018-05
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-28
• Last Update Posted: 2018-07-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Nimustine	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.
Treatment	Bevacizumab	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.

Primary Outcome Measures

Name	Time	Method
All cause response to treatment	3 weeks	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.

Secondary Outcome Measures

Name	Time	Method
All cause mortality	One year
All cause severe toxicities	3 weeks	All toxicities will be assessed and graded according to CTCAE v4.03
All cause disease progression	3 weeks	Progression disease will be evaluated according to the RANO criteria

Trial Locations

Locations (1)

Huashan hospital, Fudan University; 🇨🇳 Shanghai, Shanghai, China