NCT02698280

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
23

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2015

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2015

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

February 20, 2016

Completed
12 days until next milestone

First Posted

Study publicly available on registry

March 3, 2016

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2018

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2018

Completed
Last Updated

July 31, 2018

Status Verified

July 1, 2018

Enrollment Period

2.5 years

First QC Date

February 20, 2016

Last Update Submit

July 28, 2018

Conditions

Glioblastoma

Keywords

BevacizumabNimustinePathology, Molecular

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • All cause mortality

    One year

  • All cause disease progression

    3 weeks

  • All cause severe toxicities

    3 weeks

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Drug: BevacizumabDrug: Nimustine

Interventions

BevacizumabDRUG

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

Also known as: Avastin
Treatment
NimustineDRUG

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

Treatment

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Huashan hospital, Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Related Publications (5)

  • 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.

    PMID: 18784279BACKGROUND

  • 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.

    PMID: 18352856BACKGROUND

  • 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.

    PMID: 25035291BACKGROUND

  • 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.

    PMID: 24722048BACKGROUND

  • 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.

    PMID: 25081751BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Interventions

BevacizumabNimustine

Condition Hierarchy (Ancestors)

AstrocytomaGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsNitrosourea CompoundsUreaAmidesOrganic ChemicalsNitroso Compounds

Study Officials

  • Yu Yao, MD, PhD

    Department of Neurosurgery, Huashan hospital

    STUDY CHAIR

  • Daoying Geng, MD

    Department of Radiology, Huashan hospital

    STUDY CHAIR

  • Xiaojie Ding, MD

    Department of Neurosurgery, Huashan hospital

    PRINCIPAL INVESTIGATOR

  • Jianbo Wen, MD

    Department of Radiology, Huashan hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Resident

Study Record Dates

First Submitted

February 20, 2016

First Posted

March 3, 2016

Study Start

July 1, 2015

Primary Completion

January 1, 2018

Study Completion

May 1, 2018

Last Updated

July 31, 2018

Record last verified: 2018-07

Locations

CN(1)