Clinical trial NCT00268359: Bevacizumab and Irinotecan in Treating Patients With Recurrent or Refractory Gliomas
Official title: Bevacizumab in Combination With Irinotecan for Malignant Gliomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult glioblastoma
adult gliosarcoma
recurrent adult brain tumor
adult giant cell glioblastoma
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-12-22
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with irinotecan may kill more tumors cells.

PURPOSE: This phase II trial is studying the side effects of bevacizumab and how well giving bevacizumab together with irinotecan works in treating patients with recurrent or refractory gliomas.

Detailed description: OBJECTIVES:

Primary

* Determine the safety of bevacizumab and irinotecan hydrochloride in patients with recurrent or refractory grade 3 or 4 malignant gliomas.

Secondary

* Determine the activity of this regimen, in terms of progression-free survival, in these patients.

OUTLINE: Patients receive bevacizumab and irinotecan hydrochloride every 2 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 68 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed primary grade 3 or 4 malignant glioma of 1 of the following types:

  * Glioblastoma multiforme
  * Gliosarcoma
  * Anaplastic astrocytoma
  * Anaplastic oligodendroglioma
* Patients with recurrent disease whose original diagnostic pathology confirmed malignant glioma will not need re-biopsy
* Measurable recurrent or residual primary disease on contrast-enhanced MRI or CT scan
* Failed ≥ 1 prior chemotherapy regimen (with or without radiotherapy)

PATIENT CHARACTERISTICS:

* Karnofsky performance status 60-100%
* Hematocrit \> 29%
* Absolute neutrophil count \> 1,500/mm\^3
* Platelets \> 125,000/mm\^3
* Serum SGOT and bilirubin \< 1.5 times upper limit of normal
* Creatinine \< 1.5 mg/dL
* Urine protein:creatinine ratio ≤ 1.0
* Blood pressure ≤ 150/100 mmHg
* No unstable angina
* No New York Heart Association class II or greater congestive heart failure
* No myocardial infarction within the past 6 months
* No stroke within the past 6 months
* No clinically significant peripheral vascular disease
* No evidence of bleeding diathesis or coagulopathy
* No significant traumatic injury within the past 28 days

PRIOR CONCURRENT THERAPY:

* At least 4 weeks must have elapsed since prior chemotherapy or radiotherapy unless there is unequivocal evidence of tumor progression
* At least 6 weeks since prior surgical resection
* No previous major surgical procedures or open biopsies within 28 days prior to study entry
* No previous minor surgical procedures, fine needle aspirations, or core biopsies within 7 days prior to study entry
* No anticipated need for major surgical procedures during the course of the study
* No concurrent aspirin, non-steroidal anti-inflammatory drugs, or clopidogrel

Primary outcomes:
measure: Safety
measure: Activity in terms of progression-free survival
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Duke Cancer Institute
name: James J. Vredenburgh, MD
role: STUDY_CHAIR
References:
citation: Desjardins A, Reardon DA, Herndon JE 2nd, Marcello J, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Bailey L, Bigner DD, Friedman AH, Friedman HS, Vredenburgh JJ. Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas. Clin Cancer Res. 2008 Nov 1;14(21):7068-73. doi: 10.1158/1078-0432.CCR-08-0260.
citation: Sathornsumetee S, Cao Y, Marcello JE, Herndon JE 2nd, McLendon RE, Desjardins A, Friedman HS, Dewhirst MW, Vredenburgh JJ, Rich JN. Tumor angiogenic and hypoxic profiles predict radiographic response and survival in malignant astrocytoma patients treated with bevacizumab and irinotecan. J Clin Oncol. 2008 Jan 10;26(2):271-8. doi: 10.1200/JCO.2007.13.3652.
citation: Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Dowell JM, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Wagner M, Bigner DD, Friedman AH, Friedman HS. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007 Feb 15;13(4):1253-9. doi: 10.1158/1078-0432.CCR-06-2309.