Bevacizumab in Treating Patients With Recurrent or Progressive Glioma

• ClinicalTrials.gov Identifier: NCT00337207
• Recruitment Status: Completed
• First Posted: June 15, 2006
• Results First Posted: November 19, 2012
• Last Update Posted: February 7, 2020
• Sponsor: Northwestern University
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Jeffrey Raizer, Northwestern University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Brain and Central Nervous System Tumors	Biological: bevacizumab	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 55 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Safety Study of Bevacizumab in Patients With Multiple Recurrent or Progressive Malignant Gliomas
• Actual Study Start Date: March 2006
• Actual Primary Completion Date: November 2008
• Actual Study Completion Date: May 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Avastin	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.

Outcome Measures

Primary Outcome Measures :

1. Safety of Treatment [ Time Frame: From treatment initiation, throughout treatment and up to 30 days post-treatment, for up to 1 year. ]

   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

2. Progression-free Survival at 6 Months [ Time Frame: After all patients have surpassed the 6 month post-treatment timepoint ]
   The number of patients experiencing progression free survival (PFS) was calculated at the 6-month time point.
3. Tumoral Blood Flow Changes [ Time Frame: Before and after treatment ]
   To assess changes in tumoral blood flow based on MR Perfusion and tissue changes by MR spectroscopy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Illinois

Hematology-Oncology Associates of Illinois

Chicago, Illinois, United States, 60611-2998

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States, 60611-3013

Sponsors and Collaborators

Northwestern University

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jeffrey J. Raizer, MD; Robert H. Lurie Cancer Center

More Information

Publications of Results:

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.

• Responsible Party: Jeffrey Raizer, Jeffrey Raizer, MD, Northwestern University
• ClinicalTrials.gov Identifier: NCT00337207
• Other Study ID Numbers: NU 05C3; NU-05C3 ( Other Identifier: Northwestern University Cancer Center ); STU00005237 ( Other Identifier: Northwestern University IRB )
• First Posted: June 15, 2006
• Results First Posted: November 19, 2012
• Last Update Posted: February 7, 2020
• Last Verified: January 2020

Keywords provided by Jeffrey Raizer, Northwestern University:

adult glioblastoma; adult gliosarcoma; recurrent adult brain tumor; adult anaplastic astrocytoma; adult giant cell glioblastoma

Additional relevant MeSH terms:

Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplasms; Neoplasms by Site; Nervous System Diseases; Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors