Know Cancer

forgot password

Avastin in Combination With Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas

Phase 2
18 Years
Not Enrolling
Glioblastoma, Gliosarcoma

Thank you

Trial Information

Avastin in Combination With Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas

Subjects have histologically confirmed WHO gr IV primary malignant glioma that is
unresectable/multifocal. This is Phase II study where up to 41 subjects will receive up to 4
cycles of Avastin & Temozolomide. Avastin administered at 10 mg/kg every 14 days beginning a
minimum of 7 days after biopsy/28 days after craniotomy. Temozolomide dosed at 200 mg/m2
daily for 5 days in 28-day cycle. Patients will receive up to 4 cycles of Avastin &
Temozolomide, then proceed with standard XRT. Study will use 2-stage "minimax" study design
in which 21 subjects are accrued during 1st stage, with possibility that additional 20
patients accrued during 2nd stage. In initial Phase I & II trials, 4 potential
Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic
events, & hemorrhage. Avastin-associated adverse events in Phase III trials include
congestive heart failure, GI perforations, wound healing complications, & arterial
thromboembolic events. Most common toxicity associated with Temozolomide has been mild

Inclusion Criteria:

Patients have histologically confirmed diagnosis of WHO gr IV primary malignant glioma.
Patients will be unresectable or have multifocal disease.

- Age ≥ 18years & life expectancy of >12 weeks

- Evidence of measurable primary CNS neoplasm on contrast enhanced MRI.

- Interval of <1 week between prior biopsy/4 weeks from surgical resection & enrollment
on protocol

- Karnofsky ≥60%

- Hemoglobin ≥9g/dl, ANC ≥1,500 cells/microliter, platelets ≥125,000 cells/microliter

- Serum creatinine ≤1.5 mg/dl, serum SGOT & bilirubin ≤1.5 x ULN

- For patients on corticosteroids, they must have been on stable dose for 1 week prior
to entry, if clinically possible, & dose should not be escalated over entry dose

- Signed informed consent approved by IRB prior to patient entry

- No evidence of > grade 1 CNS hemorrhage on baseline MRI/CT scan

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

Exclusion Criteria:

- Pregnancy/breast feeding

- Co-medication that may interfere with study results

- Active infection requiring IV antibiotics

- Prior or current Treatment w XRT/chemo for brain tumor, irrespective of grade of

- Evidence of > grade 1 CNS hemorrhage on baseline MRI or CT scan

Avastin-Specific Concerns:

- Inadequately controlled hypertension

- Any prior history of hypertensive crisis/hypertensive encephalopathy

- New York Heart Association Grade II or > congestive heart failure

- History of myocardial infarction/unstable angina < 6 months prior to study enrollment

- History of stroke/transient ischemic attack < 6 months prior to study enrollment

- Significant vascular disease

- Symptomatic peripheral vascular disease

- Evidence of bleeding diathesis/coagulopathy

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

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

- History of abdominal fistula, GI perforation, /intra-abdominal abscess <6 months
prior to study enrollment

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

- Proteinuria at screening as demonstrated by either

- UPC ratio ≥1.0 at screening OR

- Urine dipstick for proteinuria ≥2+

- Known hypersensitivity to any component of Avastin

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

- Current, ongoing treatment with full-dose warfarin or its equivalent

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response Rate

Outcome Description:

The proportion of subjects with complete or partial response as determined by a modification of the RANO (Response Assessment in Neuro-Oncology) criteria. A confirmation of response was not required. Complete Response was defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks. Partial Response was defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks.

Outcome Time Frame:

4 months

Safety Issue:


Principal Investigator

Katherine B Peters, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University Health System


United States: Institutional Review Board

Study ID:




Start Date:

August 2007

Completion Date:

May 2012

Related Keywords:

  • Glioblastoma
  • Gliosarcoma
  • Glioma
  • Temozolomide
  • Temodar
  • Avastin
  • Bevacizumab
  • GBM
  • Gliosarcoma
  • Multifocal GBM
  • Brain tumor
  • Unresectable GBM
  • Glioblastoma multiforme
  • Glioblastoma
  • Gliosarcoma



Duke University Health System Durham, North Carolina  27705