Bevacizumab in Treating Patients With Recurrent or Progressive Glioma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

A Phase II Safety Study of Bevacizumab in Patients With Multiple Recurrent or Progressive Malignant Gliomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00337207
• Other study ID #: NU 05C3
• Secondary ID: NU-05C3STU000052
• Status: Completed
• Phase: Phase 2
• Start date: March 2006
• Est. completion date: May 2009

Study information

• Verified date: January 2020
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: May 2009
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Biological:
• bevacizumab
Bevacizumab 15 mg/kg every 3 weeks over 30 to 90 minutes. One cycle = 3 weeks. Treatment continues until progressive disease or unacceptable toxicity.

Locations

Country	Name	City	State
United States	Hematology-Oncology Associates of Illinois	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of Treatment	Safety of treatment will be defined by the number of patients that experience grade 3 and 4 adverse events where causal relationship with bevacizumab cannot be completely ruled out. Adverse events will be graded using Common Terminology Criteria for Adverse Events v3.0 (CTCAE) where: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE	From treatment initiation, throughout treatment and up to 30 days post-treatment, for up to 1 year.
Primary	Progression-free Survival at 6 Months	The number of patients experiencing progression free survival (PFS) was calculated at the 6-month time point.	After all patients have surpassed the 6 month post-treatment timepoint
Primary	Tumoral Blood Flow Changes	To assess changes in tumoral blood flow based on MR Perfusion and tissue changes by MR spectroscopy.	Before and after treatment