Bevacizumab and Nimustine in Patients With Recurrent High Grade Glioma

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02698280
• Other study ID #: KY-2015-289; 02
• Status: Completed
• Phase: Phase 2
• Start date: July 2015
• Est. completion date: May 2018

Study information

• Verified date: July 2018
• Source: Huashan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: May 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• Bevacizumab
Bevacizumab is administered intravenously at 5mg/kg every 3 weeks.
• Nimustine
Nimustine is administered intravenously at 90mg/m^2 to 110mg/m^2 every 6 weeks.

Locations

Country	Name	City	State
China	Huashan hospital, Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Huashan Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

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. — View 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. — View 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 . Review. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	All cause mortality		One year
Secondary	All cause disease progression	Progression disease will be evaluated according to the RANO criteria	3 weeks
Secondary	All cause severe toxicities	All toxicities will be assessed and graded according to CTCAE v4.03	3 weeks