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

January 14, 2013 updated by: David M. Brizel, MD

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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:

  • MR Imaging/Spectroscopy to be done at baseline, end of lead-in phase, end of week 1 of chemoRT, and end of chemoRT
  • Angiogenic and EGFR related cytokines. Specifically, blood samples will be obtained to assay levels of VEGF, b-FGF, IL-8, D-dimer, EGF, TGF. These samples will be obtained on the same dates as the MR studies with an additional set of samples obtained at the midpoint of the lead in phase of treatment (day -7).

Clinical Assessments:

  • All patients will undergo a minimum of once weekly interval history and physical examination including fiberoptic pharyngoscopy/laryngoscopy when indicated in the Department of Radiation Oncology to monitor for side effects and response to treatment as per standard routine for the care of patients with head and neck cancer.
  • Patient compliance with Tarceva administration monitored via diary MRI/MRS (Magnetic Resonance Spectroscopy) DE-MRI

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Department of Radiation Oncology; Duke University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Locally advanced squamous carcinoma of the head and neck (AJCC stages II/IV, M0, and excluding T1N1 and T1N2) undergoing curative intent concurrent chemoradiation.
  • Previous treatment of any sort other than a biopsy is not allowed.

  • Eligible anatomic sites:

    • oral cavity
    • oropharynx
    • hypopharynx
    • supraglottic
    • glottic larynx
  • KPS > 60

Exclusion Criteria:

  • Nasopharynx primary
  • History of malignancy other than basal cell skin cancer.
  • History of claudication, bleeding, or thromboembolic disorders. Patients receiving heparin or Coumadin therapy are ineligible.
  • Primary tumor or lymph node encasement of the carotid artery
  • Blood pressure of >150/100 mmHg
  • Unstable angina
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of myocardial infarction within 6 months
  • History of stroke within 6 months
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0; anticipation of need for major surgical procedure during the course of the study.
  • Minor surgical procedures, fine needle aspirations, or core biopsies within 7 days prior to Day 0
  • Pregnant (positive pregnancy test) or lactating
  • Urine protein : creatinine ratio ≥ 1.0 at screening
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
  • Serious, non-healing wound, ulcer, or bone fracture
  • AST, ALT, or bilirubin > 1.5 x normal
  • PT or PTT > 1.5 x normal
  • Platelets < 100,000
  • WBC < 2000
  • Hgb < 10
  • Creatinine clearance < 60 mL/hr
  • Refusal to provide written informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ChemoRadiotherapy
Radiation Therapy concurrent with cisplatin chemotherapy, Avastin and Tarceva
Radiation: Chemoradiotherapy
External beam radiation daily (M-F)
Drug: Cisplatin
Cisplatin week 1 and 5 of radiation
Drug: Bevacizumab
Bevacizumab (Avastin) day 1 of weeks 1, 3, and 5 of radiation
Other Names:
  • Avastin
Drug: Erlotinib
Erlotinib daily during radiation
Other Names:
  • Tarceva

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor Resolution
Time Frame: Within 30 days of completing RT
Complete response (resolution) of tumor on clinical exam.
Within 30 days of completing RT

Secondary Outcome Measures

Outcome Measure
Time Frame
Local Regional Control
Time Frame: 1 yr following chemoradiation
1 yr following chemoradiation
Failure Free Survival
Time Frame: 3 yrs
3 yrs

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

David M. Brizel, MD

Collaborators

Genentech, Inc.
OSI Pharmaceuticals

Investigators

  • Principal Investigator: David M Brizel, MD, Department of Radiation Oncology; Duke University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2005

Primary Completion (Actual)

May 1, 2009

Study Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

August 29, 2005

First Submitted That Met QC Criteria

August 29, 2005

First Posted (Estimate)

September 1, 2005

Study Record Updates

Last Update Posted (Estimate)

January 18, 2013

Last Update Submitted That Met QC Criteria

January 14, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00008840
  • 7077 (Other Identifier: Legacy IRB number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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