Clinical trial NCT00612339: Avastin in Combination With Temozolomide for Unresectable or Multifocal GBMs and Gliosarcomas
Official title: Avastin in Combination With Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Gliosarcoma
Keywords: Glioma
Temozolomide
Temodar
Avastin
Bevacizumab
GBM
Gliosarcoma
Multifocal GBM
Brain tumor
Unresectable GBM
Glioblastoma multiforme
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Schering-Plough
First posted: 2008-02-11
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary objective- To determine efficacy of Avastin, 10 mg/kg every other week, in combination with standard 5-day temozolomide in terms of response rate.

Secondary objective- To determine safety of Avastin \& Temozolomide in unresectable glioblastoma patients

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Response Rate
timeFrame: 4 months
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
Study officials:
affiliation: Duke Health
name: Katherine B Peters, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: