Clinical trial NCT00337207: Bevacizumab in Treating Patients With Recurrent or Progressive Glioma
Official title: A Phase II Safety Study of Bevacizumab in Patients With Multiple Recurrent or Progressive Malignant Gliomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: adult glioblastoma
adult gliosarcoma
recurrent adult brain tumor
adult anaplastic astrocytoma
adult giant cell glioblastoma
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-06-15
Enrollment: 55
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: 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.

PURPOSE: This phase II trial is studying how well bevacizumab works in treating patients with recurrent or progressive glioma.

Detailed description: OBJECTIVES:

* Determine the safety of single-agent bevacizumab in the treatment of patients with recurrent or progressive malignant glioma.
* Determine the efficacy of bevacizumab, in terms of progression-free survival at 6 months, in these patients.
* Assess changes in tumoral blood flow based on magnetic resonance (MR) perfusion and tissue changes by MR spectroscopy.

OUTLINE: This is a pilot study.

Patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed malignant glioma, including the following:

  * Glioblastoma multiforme
  * Gliosarcoma
  * Anaplastic astrocytoma or anaplastic glioma
  * Malignant glioma not otherwise specified
* Evidence of tumor recurrence or progression by MRI or CT scan with contrast

  * CT scan or MRI must be performed ≤ 96 hours post-operatively (≤ 2 weeks prior to study registration) or 4-6 weeks post-operatively to assess residual disease in patients who have undergone recent resection of recurrent or progressive tumor

    * Steroid dosage must have been stable for ≥ 5 days
* Failed ≥ 1 prior systemic treatment with chemotherapy or biologic agents (excluding polifeprosan 20 with carmustine implant \[Gliadel wafers\])
* Failed prior external-beam radiotherapy
* If received prior interstitial brachytherapy or stereotactic radiosurgery, true progressive disease (rather than radiation necrosis) must be confirmed by positron emission tomography, single-photon emission computer tomography with thallium, magnetic resonance (MR) spectroscopy, MR perfusion, or surgical documentation

PATIENT CHARACTERISTICS:

* Karnofsky performance status 70-100%
* Life expectancy \> 8 weeks
* WBC \> 3,000/mm³
* Absolute neutrophil count \> 1,500/mm³
* Platelet count \> 100,000/mm³
* Hemoglobin \> 10 g/dL (transfusion allowed)
* SGOT and SGPT \< 1.5 times upper limit of normal (ULN)
* Bilirubin \< 1.5 times ULN
* Creatinine \< 1.5 mg/dL
* Blood pressure ≤ 150/100 mm Hg
* No unstable angina
* No New York Heart Association class II-IV congestive heart failure
* No stroke or myocardial infarction within the past 6 months
* No clinically significant peripheral vascular disease
* No evidence of bleeding diathesis or coagulopathy
* Urine protein:creatinine ratio \< 1.0
* No significant medical illness that would preclude study participation or cannot be adequately controlled with appropriate therapy
* No other serious medical illness or infection
* No disease that would obscure toxicity or dangerously alter drug metabolism
* No significant traumatic injury within the past 28 days
* No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
* No serious, nonhealing wound, ulcer, or bone fracture
* No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix) unless cancer is in complete remission and patient is off all therapy for that cancer for ≥ 3 years
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* More than 4 weeks since prior surgery for recurrent or progressive disease and recovered
* More than 28 days since prior major surgical procedure or open biopsy
* At least 4 weeks since prior cytotoxic therapy (6 weeks for nitrosoureas)
* At least 2 weeks since prior vincristine
* At least 3 weeks since prior procarbazine hydrochloride
* At least 1 week since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin)

  * Radiosensitizer does not count
* At least 4 weeks since prior experimental biologic agents (e.g., epidermal growth factor receptor \[EGFR\] inhibitors)
* More than 7 days since prior minor surgery, such as fine-needle aspirations or core biopsies
* No concurrent combination anti-retroviral therapy for HIV-positive patients
* No concurrent enzyme-inducing anticonvulsants (EIACs)

  * Patients on EIACs must switch to nonenzyme-inducing convulsants ≥ 2 weeks prior to study enrollment

Primary outcomes:
measure: Safety of Treatment
timeFrame: From treatment initiation, throughout treatment and up to 30 days post-treatment, for up to 1 year.
measure: Progression-free Survival at 6 Months
timeFrame: After all patients have surpassed the 6 month post-treatment timepoint
measure: Tumoral Blood Flow Changes
timeFrame: Before and after treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Hematology-Oncology Associates of Illinois
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Jeffrey J. Raizer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Raizer JJ, Gallot L, Cohn R, et al.: A phase II safety study of bevacizumab in patients with multiple recurrent or progressive malignant gliomas. [Abstract] J Clin Oncol 25 (Suppl 18): A-2079, 94s, 2007.