Phase II Trial of Bevacizumab, Cetuximab, and Cisplatin With IMRT (Intensity-Modulated Radiation Therapy) for Patients With Stage III/IV Head and Neck Squamous Cell Carcinoma
- Stage III/IV HNSCC without distant metastasis. Patients with stage II squamous cell
carcinoma of the hypopharynx will also be eligible
- Adequate renal function, with serum creatinine ≤ 1.5 mg/dL. Patients with serum
creatinine > 1.5 mg/dL may be eligible if calculated creatinine clearance > or = to
55 ml/min by Cockcroft and Gault equation (or 24-hour urine collection).
- Age > or = to 18 years.
- Karnofsky performance status > or = to 70%
- Adequate bone marrow function: absolute neutrophil count > or = to 1,500/ platelets
> or = to 100,000/ul, hemoglobin > or = to 9 gm/dl
- Adequate hepatic function: Total bilirubin ≤ 1.5 X ULN (patients with Gilbert's
syndrome as the cause of hyperbilirubinemia may be eligible if total bilirubin ≤ 2.5
X ULN), aspartate aminotransferase (AST) ≤ 2.5 X ULN, alanine aminotransferase (ALT)
≤ 2.5 X ULN, alkaline phosphatase ≤ 2.5 X ULN.
- Men and women of childbearing potential must be willing to consent to using effective
contraception while on treatment and for at least 3 months thereafter.
- Patients must have ability to understand and the willingness to sign a written
informed consent document.
- Prior radiation therapy for HNSCC
- Prior treatment of HNSCC with bevacizumab or other agents specifically targeting VEGF
- Prior treatment of HNSCC with cetuximab or other agents specifically targeting EGFR
- Other active malignancy, other than indolent malignancies, which the investigator
determines are unlikely to interfere with treatment or efficacy analysis. For
example, patients with non-melanoma skin cancer, in situ carcinoma of the cervix, or
prostate cancer within the no current biochemical (PSA) or radiologic evidence of
disease may enroll.
- Patients with nasopharyngeal carcinoma
- Patients who will receive amifostine as part of the radiation treatment plan
- Patients with skin breakdown/ulceration (CTCAE version 3.0, grade 2 or higher).
- Patients with hearing loss requiring hearing aid or intervention (i.e. interfering in
a clinically significant way with activities of daily living).
- Patients with multifocal peripheral sensory alterations or paresthesias (including
tingling) interfering with function, per patient report (example: activities of daily
- Any prior documented history of transient ischemic attack (TIA) or cerebrovascular
- History of unstable angina or myocardial infarction (MI) within the last year.
- Urine protein: creatinine (UPC) ratio > or = to 1.0 at screening. A random urine
sample is collected. Total protein (mg/dL) and spot creatinine (mg/dL) are ordered
for this sample. The UPC ratio is calculated from the results of these tests.
- International normalized ratio (INR) > 1.5 or activated partial thromboplastin time
(aPTT) > 1.5 X upper limits of normal (ULN)
- Current use of warfarin, current use of heparin or low-molecular weight heparin,
chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory
medications known to inhibit platelet function.
- Patients with gross hemoptysis or hematemesis (defined as bright red blood of 1
teaspoon of more) within 28 days prior to Day 0 protocol treatment will be excluded
from this trial. Patients with incidental blood mixed with phlegm are not excluded.
- Esophageal varices, non-healing ulcer, wound, or bone fracture are exclusion
criteria. However, patients with skin breakdown overlying malignant neck
lymphadenopathy may be eligible, at the discretion of the investigator.
- Anatomic lesion that increases the risk of serious hemorrhage, such as encasement or
invasion of major blood vessels by primary tumor and/or by involved lymph nodes
- Blood pressure of > 150/100 mmHg
- New York Heart Association (NYHA) Grade II or greater congestive heart failure.
- Clinically significant peripheral vascular disease
- History of bleeding diathesis or hemorrhagic disorder, or coagulopathy.
- Major surgical procedure or significant traumatic injury within 28 days prior to
treatment with bevacizumab
- Core biopsy within 7 days prior to treatment with bevacizumab.
- Minor surgical procedures such as fine needle aspirations or placement of
percutaneous gastrostomy tube (PEG) less than 7 days prior to treatment with
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior enrollment.
- Inability to comply with study and/or follow-up procedures
- Women who are pregnant or lactating