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

• Status: Completed
• Trial end date: 2010-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: David M. Brizel, MD
• Collaborators: Genentech, Inc.; OSI Pharmaceuticals
• Treatments: Bevacizumab; Cisplatin; Erlotinib Hydrochloride

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