Clinical trial NCT02698280: Bevacizumab and Nimustine in Patients With Recurrent High Grade Glioma
Official title: Phase II Study of Bevacizumab and Nimustine in Patients With Recurrent High Grade Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Keywords: Bevacizumab
Nimustine
Pathology, Molecular
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2016-03-03
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: All cause response to treatment
timeFrame: 3 weeks
Secondary outcomes:
measure: All cause mortality
timeFrame: One year
measure: All cause disease progression
timeFrame: 3 weeks
measure: All cause severe toxicities
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan hospital, Fudan University
state: Shanghai
Study officials:
affiliation: Department of Neurosurgery, Huashan hospital
name: Yu Yao, MD, PhD
role: STUDY_CHAIR
affiliation: Department of Radiology, Huashan hospital
name: Daoying Geng, MD
role: STUDY_CHAIR
affiliation: Department of Neurosurgery, Huashan hospital
name: Xiaojie Ding, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Radiology, Huashan hospital
name: Jianbo Wen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vredenburgh JJ, Desjardins A, Reardon DA, Friedman HS. Experience with irinotecan for the treatment of malignant glioma. Neuro Oncol. 2009 Feb;11(1):80-91. doi: 10.1215/15228517-2008-075. Epub 2008 Sep 10.
citation: 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.
citation: 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.
citation: 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.
citation: 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.