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

This study has been completed.
Sponsor:
Collaborators:
Genentech
OSI Pharmaceuticals
Information provided by (Responsible Party):
David M. Brizel, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00140556
First received: August 29, 2005
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Pharynx Cancer
Radiation: Chemoradiotherapy
Drug: Cisplatin
Drug: Bevacizumab
Drug: Erlotinib
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Concurrent Angiogenic and EGFR Blockade in Conjunction With Curative Intent Chemoradiation for Locally Advanced Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Tumor Resolution [ Time Frame: Within 30 days of completing RT ] [ Designated as safety issue: No ]
    Complete response (resolution) of tumor on clinical exam.


Secondary Outcome Measures:
  • Local Regional Control [ Time Frame: 1 yr following chemoradiation ] [ Designated as safety issue: No ]
  • Failure Free Survival [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: August 2005
Study Completion Date: April 2010
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Avastin
Drug: Erlotinib
Erlotinib daily during radiation
Other Name: Tarceva

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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00140556

Locations
United States, North Carolina
Department of Radiation Oncology; Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
David M. Brizel, MD
Genentech
OSI Pharmaceuticals
Investigators
Principal Investigator: David M Brizel, MD Department of Radiation Oncology; Duke University Medical Center
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: David M. Brizel, MD, Professor, Radiation Oncology, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00140556     History of Changes
Other Study ID Numbers: Pro00008840, 7077
Study First Received: August 29, 2005
Results First Received: August 19, 2010
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
head and neck cancer
targeted therapy
bevacizumab
erlotinib
Tarceva
radiotherapy
concurrent chemotherapy
pharynx cancer
tonsil cancer
hyperfractionation
angiogenesis
epidermal growth factor
vascular endothelial growth factor
magnetic resonance spectroscopy
cancer of the head and neck
upper aerodigestive tract neoplasms
pharynx neoplasms

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Bevacizumab
Cisplatin
Erlotinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Radiation-Sensitizing Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014