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Phase II Study of Bevacizumab Plus Either Temozolomide or Etoposide for (GBM) Patients Who Have Failed Bevacizumab Plus Irinotecan

Phase 2
18 Years
Not Enrolling
Glioblastoma, Gliosarcoma

Thank you

Trial Information

Phase II Study of Bevacizumab Plus Either Temozolomide or Etoposide for (GBM) Patients Who Have Failed Bevacizumab Plus Irinotecan

This is exploratory, two-arm, phase II study designed to assess anti-tumor activity of bev +
either daily temozolomide/etoposide among GBM pts w progressive disease following bev +
irinotecan. About 48 participants w recurrent GBM will take part in this study.
Approximately 24 participants will receive bev plus temozolomide & approximately 24 will
receive bev + etoposide. Pts must have confirmed diagnosis of GBM & radiographic evidence of
recurrence following prior therapy bev + irinotecan. 24 pts will be enrolled onto each arm
of this single-stage study. If 4 or more of these 24 pts live 6/more months without disease
progression, treatment regimen will be considered worthy of further investigation.
Otherwise, treatment regimen will be determined not worthy of further investigation within
pt population. Type I & II error rates associated w testing are 0.030 & 0.115 respectively.
Management guidelines dose reduction/interruption for temo, etoposide, & bev.

Inclusion Criteria:

- Pts have confirmed diagnosis of GBM & radiographic evidence of recurrence following
prior therapy w bev + irinotecan

- Age >18 yrs

- Interval of >4 wks between prior surgical resection/1 week from stereotactic biopsy

- Interval of >12 wks from end of prior external beam radiation therapy (XRT) unless
there is new area of enhancement consistent w recurrent tumor outside of XRT
field,/there are progressive changes on MRI on >2 consecutive MRI scans >4wks apart,
/there is biopsy-proven tumor progression

- Interval of >4 wks from prior chemo / investigational agent unless pt has recovered
from all anticipated toxicities associated w that therapy.

- Eastern Cooperative Oncology Group (ECOG) 0-1

- Hematocrit >29percent, absolute neutrophil count (ANC)>1,000 cells/ml l, platelets >
100,000 cells/ml l

- Serum creatinine<1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) &
bilirubin<1.5 times upper limit of normal (ULN)

- Signed informed consent approved by Institutional Review Board (IRB) prior to pt

- No evidence of hemorrhage on baseline MRI/CT scan other than those that are stable

- If sexually active, pts will take contraceptive measures for duration of treatments

Exclusion Criteria:

- Co-medication that may interfere w study results

- Active infection requiring intravenous antibiotics

- Progression to daily etoposide/progression to daily temo

- Gr3/greater toxicity related to prior bev therapy,/prior temozolomide/etoposide

- Requires therapeutic anti-coagulation with warfarin.

- Inability to comply w study and/or follow-up procedures

- Current, recent,/planned participation in experimental drug study other than
Genentech-sponsored bev cancer study

- Inadequately controlled hypertension

- Any prior history of hypertensive crisis/hypertensive encephalopathy

- New York Heart Association (NYHA) Gr II/greater congestive heart failure

- History of myocardial infarction (MI)/unstable angina within 6 mths prior to study

- History of stroke/transient ischemic attack within 6 mths prior to study enrollment

- Significant vascular disease

- Symptomatic peripheral vascular disease

- Evidence of bleeding diathesis or coagulopathy

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to study enrollment or anticipation of need for major surgical procedure during
the course of the study

- Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 days prior to study enrollment

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study enrollment

- Serious, non-healing wound, ulcer, or bone fracture

- Proteinuria at screening as demonstrated by either:

- urine protein:creatinine (UPC) ratio >1.0 at screening /

- Urine dipstick for proteinuria ≥ 2+

- Known hypersensitivity to any component of bevacizumab

- Pregnant or lactating. Use of effective means of contraception in subjects of
child-bearing potential

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The Primary Outcome Measure is 6 Month Progression-free Survival.

Outcome Description:

Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

David A. Reardon, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University Health System


United States: Institutional Review Board

Study ID:




Start Date:

April 2008

Completion Date:

September 2012

Related Keywords:

  • Glioblastoma
  • Gliosarcoma
  • Glioblastoma
  • Gliosarcoma
  • GBM
  • Bevacizumab
  • Avastin
  • Etoposide
  • Brain tumor
  • Irinotecan
  • Glioblastoma multiforme
  • Temodar
  • Temozolomide
  • Etopophos
  • Toposar
  • VePesid
  • VP-16
  • Camptosar
  • Glioblastoma
  • Gliosarcoma



Duke University Health SystemDurham, North Carolina  27705