Back to results

Bevacizumab and Nimustine in Patients With Recurrent High Grade Glioma

Primary Purpose

Glioblastoma

Status

Completed

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Bevacizumab

Nimustine

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Bevacizumab, Nimustine, Pathology, Molecular

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Huashan hospital, Fudan University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

All cause mortality

All cause disease progression

Progression disease will be evaluated according to the RANO criteria

All cause severe toxicities

All toxicities will be assessed and graded according to CTCAE v4.03

Full Information

NCT ID

NCT02698280

First Posted

February 20, 2016

Last Updated

July 28, 2018

Sponsor

Huashan Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02698280

Brief Title

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

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

July 2015 (Actual)

Primary Completion Date

January 2018 (Actual)

Study Completion Date

May 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Huashan Hospital

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma

Keywords

Bevacizumab, Nimustine, Pathology, Molecular

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Other Intervention Name(s)

Avastin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Nimustine

Intervention Description

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

Primary Outcome Measure Information:

Title

All cause response to treatment

Description

Time Frame

3 weeks

Secondary Outcome Measure Information:

Title

All cause mortality

Time Frame

One year

Title

All cause disease progression

Description

Progression disease will be evaluated according to the RANO criteria

Time Frame

3 weeks

Title

All cause severe toxicities

Description

All toxicities will be assessed and graded according to CTCAE v4.03

Time Frame

3 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yu Yao, MD, PhD

Organizational Affiliation

Department of Neurosurgery, Huashan hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Daoying Geng, MD

Organizational Affiliation

Department of Radiology, Huashan hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Xiaojie Ding, MD

Organizational Affiliation

Department of Neurosurgery, Huashan hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jianbo Wen, MD

Organizational Affiliation

Department of Radiology, Huashan hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Huashan hospital, Fudan University

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200040

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

18784279

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.

Results Reference

background

PubMed Identifier

18352856

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.

Results Reference

background

PubMed Identifier

25035291

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.

Results Reference

background

PubMed Identifier

24722048

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.

Results Reference

background

PubMed Identifier

25081751

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.

Results Reference

background

Learn more about this trial

Bevacizumab and Nimustine in Patients With Recurrent High Grade Glioma

We'll reach out to this number within 24 hrs