Clinical Trial: Bevacizumab, Fluorouracil, and Hydroxyurea Plus Radiation Therapy in Treating Patients With Advanced Head and Neck Cancer

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

Official Title: A Phase I Study Of Bevacizumab (Recombinant Humanized Monoclonal Antibody To Vascular Endothelial Growth Factor) In Addition To Flourouracil And Hydroxyurea As Initial Chemotherapy With Concomitant Ra

Brief Summary: 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 deliver cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining monoclonal antibody therapy with chemotherapy and radiation therapy may be an effective treatment for head and neck cancer. This phase I trial is to see if combining bevacizumab, fluorouracil, and hydroxyurea with radiation therapy works in treating patients who have advanced head and neck cancer

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and dose-limiting toxicity of bevacizumab when given in combination with fluorouracil, hydroxyurea, and radiotherapy in patients with advanced head and neck cancer.

II. Determine the time to progression, pattern of failure, local control, and distant failure rate in patients treated with this regimen.

III. Determine the local toxic effects of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of bevacizumab.

Patients receive oral hydroxyurea every 12 hours on days 1-6, fluorouracil IV continuously on days 1-5, and bevacizumab IV over 90 minutes on day 1. Patients also undergo radiotherapy once daily on days 1-5. Patients receive filgrastim (G-CSF) subcutaneously on days 6-12. Treatment repeats every 2 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 27-39 patients will be accrued for this study within 5.4-19.5 months.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: MTD defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity assessed using NCI CTCAE version 3.0 [ Time Frame: 14 weeks ]

Original Primary Outcome:

Current Secondary Outcome:

  • Objective response rate (CR+PR) assessed using RECIST criteria [ Time Frame: Up to 9 years ]
    The associated 95% confidence interval will be determined.
  • Pattern of failure, described as locoregional, distant, or both [ Time Frame: Up to 9 years ]
  • Duration of response [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 9 years ]
  • Progression free survival [ Time Frame: From the date of registration to the date of progressive disease or death, assessed up to 9 years ]
    Will be calculated using the Kaplan-Meier method, and median progression-free and overall survival times, along with their 95% confidence intervals, will be derived using the procedure described in Brookmeyer and Crowley.
  • Overall survival [ Time Frame: From the date of registration to the date of death, assessed up to 9 years ]
    Will be calculated using the Kaplan-Meier method, and median progression-free and overall survival times, along with their 95% confidence intervals, will be derived using the procedure described in Brookmeyer and Crowley.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: September 13, 2001
Date Started: July 2001
Date Completion:
Last Updated: February 6, 2013
Last Verified: February 2013