Palifermin in Lessening Oral Mucositis in Patients Undergoing Radiation Therapy and Chemotherapy for Locally Advanced Head and Neck Cancer

• Duration of oral mucositis as measured in terms of days [ Designated as safety issue: No ]
  

• Incidence and time to onset of mucositis as measured by the WHO scale [ Designated as safety issue: No ]
  
• Change in symptom burden and pain as measured by MD Anderson Symptom Inventory-Head and Neck and Brief Pain Inventory questionnaires [ Designated as safety issue: No ]
  
• Use of nutritional support via nasogastric or percutaneous endoscopic gastrostomy feeding tubes [ Designated as safety issue: No ]
  
• Opioid analgesic usage (total dose in morphine equivalents) [ Designated as safety issue: No ]
  
• Incidence of xerostomia as measured by CTCAE v. 3.0 salivary gland changes/saliva xerostomia scale and the dry mouth/salivary gland xerostomia scale vs patient self-reporting [ Designated as safety issue: No ]
  
• Long-term effects of treatment: overall survival, progression-free survival, and incidence of second primaries [ Designated as safety issue: No ]
  
• Long-term safety [ Designated as safety issue: Yes ]
  
• Acute short-term safety [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• Compare the efficacy of palifermin vs placebo, in terms of burden of acute mucositis (defined to be 105 days [15 weeks] or less from the start of treatment), in patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing concurrent radiotherapy and chemotherapy.

Secondary

• Compare incidence and time to onset of mucositis in patients treated with these regimens.
• Compare symptom burden by patient-reported outcomes in patients treated with these regimens.
• Compare experience of pain and opioid analgesic utilization in patients treated with these regimens.
• Compare incidence of xerostomia in patients treated with these regimens.
• Correlate long-term effects of these regimens with disease outcome and survival of these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease stage (III vs IVA or IVB), tumor site (oral cavity or oropharynx vs hypopharynx or larynx), and radiotherapy technique used on study (intensity-modulated radiotherapy [IMRT] vs 3-dimensional conformal radiotherapy [3D-CRT]). Patients are randomized to 1 of 2 treatment arms.

All patients undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 42-46 (7 weeks for 3D-CRT) or days 1-5, 8-12, 15-19, 22-26, 29-33, 36-38, and 42-46 (7 weeks for IMRT). Patients also receive concurrent chemotherapy comprising cisplatin IV over 1-2 hours on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity.

• Arm I: Patients receive palifermin IV on days -3, 5, 12, and 19. Patients who continue to have ulcerative lesions after the completion of chemotherapy and radiotherapy receive palifermin IV once weekly beginning on the last day of chemoradiotherapy and continuing for up to 3 weeks.
• Arm II: Patients receive placebo IV on days -3, 5, 12, and 19. Patients who continue to have ulcerative lesions at the completion of chemotherapy and radiotherapy receive placebo IV once weekly beginning on the last day of chemoradiotherapy and continuing for up to 3 weeks.

Patients are reevaluated 8 weeks after completion of chemoradiotherapy. Patients with remaining tumor at that time may undergo a neck dissection and/or surgical resection of the tumor.

Mucositis, pain, and symptom burden are assessed at baseline, during radiotherapy, and post radiotherapy. Xerostomia is assessed at baseline, during radiotherapy, and several times after completion of study therapy.

After completion of study therapy, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 298 patients will be accrued for this study.