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


Phase 2
18 Years
N/A
Not Enrolling
Both
Glioblastoma, Gliosarcoma

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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
myelosuppression.


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
level

- 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
treatments

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
tumor

- 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:

Interventional

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:

No

Principal Investigator

Katherine B Peters, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University Health System

Authority:

United States: Institutional Review Board

Study ID:

Pro00001022

NCT ID:

NCT00612339

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

Name

Location

Duke University Health System Durham, North Carolina  27705