Bevacizumab and Nimustine in Patients With Recurrent High Grade Glioma

NCT ID: NCT02698280

Last Updated: 2018-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2018-05-31

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.

Conditions

Glioblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

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.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Bevacizumab is administered intravenously at 5mg/kg every 3 weeks.

Nimustine

Intervention Type: DRUG

Nimustine is administered intravenously at 90mg/m\^2 to 110mg/m\^2 every 6 weeks.

Interventions

Bevacizumab

Bevacizumab is administered intravenously at 5mg/kg every 3 weeks.

Intervention Type: DRUG

Nimustine

Nimustine is administered intravenously at 90mg/m\^2 to 110mg/m\^2 every 6 weeks.

Intervention Type: DRUG

Other Intervention Names

Avastin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Huashan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiaojie Ding

Resident

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yu Yao, MD, PhD

Role: STUDY_CHAIR

Department of Neurosurgery, Huashan hospital

Daoying Geng, MD

Role: STUDY_CHAIR

Department of Radiology, Huashan hospital

Xiaojie Ding, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurosurgery, Huashan hospital

Jianbo Wen, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Radiology, Huashan hospital

Locations

Huashan hospital, Fudan University

Shanghai, Shanghai Municipality, China

Countries

China

References

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Reference Type: BACKGROUND

PMID: 18784279 (View on PubMed)

Reardon DA, Wen PY, Desjardins A, Batchelor TT, Vredenburgh JJ. Glioblastoma multiforme: an emerging paradigm of anti-VEGF therapy. Expert Opin Biol Ther. 2008 Apr;8(4):541-53. doi: 10.1517/14712598.8.4.541.

Reference Type: BACKGROUND

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Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, Boerman D, de Vos FY, Dinjens WN, Enting RH, Taphoorn MJ, van den Berkmortel FW, Jansen RL, Brandsma D, Bromberg JE, van Heuvel I, Vernhout RM, van der Holt B, van den Bent MJ. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol. 2014 Aug;15(9):943-53. doi: 10.1016/S1470-2045(14)70314-6. Epub 2014 Jul 15.

Reference Type: BACKGROUND

PMID: 25035291 (View on PubMed)

Killela PJ, Pirozzi CJ, Healy P, Reitman ZJ, Lipp E, Rasheed BA, Yang R, Diplas BH, Wang Z, Greer PK, Zhu H, Wang CY, Carpenter AB, Friedman H, Friedman AH, Keir ST, He J, He Y, McLendon RE, Herndon JE 2nd, Yan H, Bigner DD. Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas. Oncotarget. 2014 Mar 30;5(6):1515-25. doi: 10.18632/oncotarget.1765.

Reference Type: BACKGROUND

PMID: 24722048 (View on PubMed)

Chan AK, Yao Y, Zhang Z, Chung NY, Liu JS, Li KK, Shi Z, Chan DT, Poon WS, Zhou L, Ng HK. TERT promoter mutations contribute to subset prognostication of lower-grade gliomas. Mod Pathol. 2015 Feb;28(2):177-86. doi: 10.1038/modpathol.2014.94. Epub 2014 Aug 1.

Reference Type: BACKGROUND

PMID: 25081751 (View on PubMed)

Other Identifiers

KY-2015-289; 02

Identifier Type: -

Identifier Source: org_study_id