Clinical Trial: Bevacizumab and Cediranib Maleate in Treating Patients With Metastatic or Unresectable Solid Tumor, Lymphoma, Intracranial Glioblastoma, Gliosarcoma or Anaplastic Astrocytoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I Clinical Trial Evaluating the Toxicity, Pharmacokinetics and Biological Effect of Intravenous Bevacizumab (Avastin TM) in Combination With Escalating Doses of Oral AZD2171 for Patients With Ad

Brief Summary: This phase I trial is studying the side effects and best dose of bevacizumab and cediranib maleate in treating patients with metastatic or unresectable solid tumor, lymphoma, intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Cediranib maleate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bevacizumab and cediranib maleate may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving bevacizumab together with cediranib maleate may kill more cancer cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the safety and toxicity profile of intravenous bevacizumab (avastin) administered in combination with oral AZD2171 (cediranib maleate) for patients with advanced malignancies.

II. To determine the pharmacokinetic profile of oral AZD2171 in combination with bevacizumab (avastin) administered to patients with advanced malignancies.

SECONDARY OBJECTIVES:

I. To evaluate the serum concentrations of Nitric Oxide (NO) and Nitric oxide synthase (NOS) among patients treated with this regimen and to correlate with VEGF expression.

II. To determine changes in the tumor vasculature detected by DCE-MRI among patients treated with this combination of VEGF receptor blocking agents.

III. To evaluate the potential predictive role of angiogenesis molecular endpoints in malignant effusion samples.

IV. To assess in a descriptive fashion the efficacy of the studied regimen.

OUTLINE: This is a dose-escalation study.

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral cediranib maleate once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bevacizumab and cediranib maleate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Safety and toxicity profile of combination bevacizumab and cediranib maleate [ Time Frame: Up to 6 weeks post-treatment ]
    The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
  • Pharmacokinetic profile of oral cediranib maleate in combination with bevacizumab [ Time Frame: Baseline and at 1, 2, 3, 4, 6, 8, and 24 hours after cediranib maleate treatment ]


    • Original Primary Outcome:

    • Maximum tolerated dose
    • Pharmacokinetics of Bevacizumab and AZD2171
    • Toxicity


    Current Secondary Outcome:

    Original Secondary Outcome:

    • Vascular endothelial growth factor expression in malignant effusions
    • Response rate
    • Association between nitric oxide and blood pressure


    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: April 9, 2007
    Date Started: May 2007
    Date Completion:
    Last Updated: February 14, 2014
    Last Verified: December 2013