Clinical Trial: Angiogenic and EGFR Blockade With Curative Chemoradiation for Advanced Head and Neck Cancer

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

Official Title: Concurrent Angiogenic and EGFR Blockade in Conjunction With Curative Intent Chemoradiation for Locally Advanced Head and Neck Cancer

Brief Summary:

Radiotherapy (RT) with concurrent chemotherapy represents the state of the art in curative intent treatment for locally advanced squamous carcinoma of the head and neck. Tumor hypoxia and high levels of angiogenesis (blood vessel formation) are associated with treatment failure. Preclinical models reveal that radiotherapy itself may induce tumor secretion of vascular endothelial growth factor (VEGF). Curability may consequently be reduced by multiple mechanisms. Over-expression of epidermal growth factor receptor (EGFR) also occurs commonly and increases the risk of treatment failure. The addition of EGFR blockade to RT alone increases the chance of a cure. Concurrent VEGF and EGFR blockade could be synergistic with one another and improve the effectiveness of concurrent chemoradiation for advanced head and neck cancer.

This study will add angiogenic and epidermal growth factor receptor (EGFR) blockade into an established program of curative intent concurrent chemoradiation for locally advanced head and neck cancer. The safety and effectiveness of delivering the drugs bevacizumab and Tarceva in conjunction with twice daily irradiation and concurrent cisplatin (CDDP) chemotherapy will be determined.


Detailed Summary:

Pre Radiation Period:

  • Bevacizumab (10 mg/kg) on days -14 and 0, or
  • Tarceva (100 mg) daily from -14-0, or
  • Bevacizumab (10 mg/kg) on days -14 and 0; Tarceva (100 mg) daily from -14-0

Chemoradiation Period:

  • Radiotherapy may be delivered via conventional 2-D, conformal 3-D, or intensity modulated (IMRT) technique as is clinically indicated. Radiotherapy and CDDP doses will be delivered uniformly to all treatment cohorts:

    • RT: 1.25 Gy BID M-F with a 6 hour interfraction interval
    • Treatment break during week 4. Total dose 70 Gy/7 weeks
    • CDDP: 33 mg/m2 M-W on weeks 1 and 5 of RT with standard DUMC hydration and anti-emetic regimens
  • Bevacizumab (10mg/kg): Monday of weeks 1, 3, 5, 7 of RT
  • Tarceva (100 mg): Daily for weeks 1-7 of treatment, except for days receiving CDDP

Safety Assessments:

  • Baseline and then weekly assessments of blood pressure and urine protein : creatinine ratios during lead in and chemoRT phases of treatment
  • Baseline carotid Doppler ultrasound evaluation
  • Carotid Doppler ultrasound evaluation 1 month post-chemoRT

Efficacy Assessments:

  • Sponsor: David M. Brizel, MD

    Current Primary Outcome: Tumor Resolution [ Time Frame: Within 30 days of completing RT ]

    Complete response (resolution) of tumor on clinical exam.


    Original Primary Outcome: Primary site complete response rate

    Current Secondary Outcome:

    • Local Regional Control [ Time Frame: 1 yr following chemoradiation ]
    • Failure Free Survival [ Time Frame: 3 yrs ]


    Original Secondary Outcome:

    • Local Regional Control
    • Failure Free Survival
    • Survival
    • Completion of full course of irradiation


    Information By: Duke University

    Dates:
    Date Received: August 29, 2005
    Date Started: August 2005
    Date Completion:
    Last Updated: January 14, 2013
    Last Verified: January 2013