A Randomized, Phase III, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Palifermin (NSC# 740548; IND # 6370) for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer Receiving Radiation Therapy With Concurrent Chemotherapy (Followed by Surgery for Selected Patients)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity,
oropharynx, hypopharynx, or larynx, meeting all of the following criteria:

- At least 2 mucosal sites of the oral cavity/oropharynx mucosa that will be
irradiated are assessable by visual transoral inspection

- Tumors of the larynx or hypolarynx are allowed only if it is anticipated that
the 2 index sites in the oral cavity/oropharynx mucosa will be irradiated

- Selected stage III (excluding T1, N1, M0), or IVA or IVB disease

- No distant metastases or stage IVC disease (any T, any N, M1)

- No prior squamous cell cancer of the head and neck

PATIENT CHARACTERISTICS:

- Zubrod performance status 0-1

- Absolute neutrophil count ≥ 1,800/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 8.0 g/dL (transfusion allowed)

- Bilirubin < 1.5 mg/dL

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 times upper
limit of normal

- Creatinine < 1.5 mg/dL

- Creatinine clearance ≥ 50 mL/min

- Able to eat at least soft solids and does not require a feeding tube for nutrition or
hydration

- Calcium normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior invasive malignancy (except nonmelanomatous skin cancer) unless disease free
for ≥ 3 years

- No severe, active co-morbidity, including any of the following:

- Symptomatic and/or uncontrolled cardiac disease (i.e., New York Heart
Association class III-IV cardiac disease)

- Transmural myocardial infarction within the past 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

- Seropositive for hepatitis B virus or hepatitis C virus

- Seropositive for HIV or confirmed AIDS

- History of pancreatitis

- Collagen vascular disease, such as scleroderma

- No prior allergic reaction or known sensitivity to any of the agents administered
during study dosing, including E. coli-derived products, such as any of the
following:

- Somatropin (somatren)

- Filgrastim (G-CSF)

- Insulin

- Interferon alfa-2a

- Neumega® Oprelvekin (interleukin-11)

- Interferon alfa-2b

- Pegfilgrastim

- Interferon beta-1b

PRIOR CONCURRENT THERAPY:

- No prior systemic chemotherapy for this cancer

- Prior chemotherapy for a different cancer is allowed

- No prior radiotherapy to a region that would result in overlap of radiation therapy
fields

- No prior radical or modified neck dissection

- No prior initial surgical treatment, excluding diagnostic biopsy of the primary site
or nodal sampling of neck disease

- No prior palifermin or other keratinocyte growth factors (i.e., velafermin or
repifermin)

- Concurrent topical anesthetics allowed

- No concurrent administration of any of the following during radiotherapy:

- 'Magic' mouthwash, 'Miracle' mouthwash, or other mouthwash solutions containing
chlorhexidine, Gelclair®, hydrogen peroxide, or diphenhydramine

- Pilocarpine hydrochloride

- Cevimeline hydrochloride

- Amifostine

- Benzydamine hydrochloride

- Interleukin-11

- Sargramostim (GM-CSF)

- Epoetin alfa

- Sucralfate in suspension form

- Tablets allowed

- Steroid rinses

- Povidone-iodine rinses

- Glutamine as a prophylactic agent for mucositis

- Other investigational agents

- Other biologic response modifiers, with the exception of hematopoietic growth
factors for the management of anemia or myelosuppression