A Study of Palifermin for the Reduction of Oral Mucositis in Subjects With Advanced Head and Neck Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of palifermin (recombinant human keratinocyte growth factor, rHuKGF) in reducing the incidence of severe oral mucositis in subjects with locally advanced head and neck cancer receiving radiotherapy with concurrent chemotherapy as adjuvant treatment for their disease.

Detailed Description
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This study is being conducted to evaluate the efficacy of palifermin administered intravenously (IV) in weekly doses (minimum of 7 weekly doses, until RT was complete) in reducing the incidence of severe (World Health Organization [WHO] grade 3 or 4) oral mucositis in subjects with locally advanced HNC receiving RT concurrent with CT (RT/CT) as adjuvant treatment for their disease (postoperative setting). This study will assess the safety and tolerability of palifermin at the dose of 120 μg/kg IV administered weekly (minimum 7 weekly doses, until RT was complete) in this subject population. This study will also evaluate the effect of palifermin on the clinical sequelae of severe OM (eg, average subject-reported mouth and throat soreness [MTS] score), and on RT-induced xerostomia in this population, as well as the long-term effects of palifermin on disease outcome and survival in this population.

Official Title
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Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Weekly Doses of Palifermin (rHuKGF) for the Reduction of Oral Mucositis in Subjects With Advanced Head and Neck Cancer Receiving Adjuvant Radiotherapy and Chemotherapy(RT/CT)

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Placebo
* Drug: Palifermin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of histologically documented squamous cell carcinoma ( AJCC [American Joint Committee on Cancer] Stage II, III, IVA or IVB) involving either the oral cavity, oropharynx, hypopharynx, or larynx,post surgical resection (R0, R1) and candidates for adjuvant RT/CT Radiation treatment field to receive planned dose of at least 50Gy to area of the oral cavity/oropharynx mucosa that can be visualized Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 Functional hematopoietic and hepato-renal systems Exclusion Criteria: Tumors of the lips, paranasal sinuses, salivary glands, or unknown primary tumors Metastatic disease (M1) Stage IV C Presence or history of any other primary malignancy (other than curatively treated in situ cervical cancer or basal cell carcinoma of the skin) History of chronic pancreatitis or episode of acute pancreatitis within the last year Prior radiation to the site of the disease, or prior chemotherapy-

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Palifermin<br>Single IV dose of palifermin at 120 μg/kg, 3 days before the start of radiotherapy plus 6 once weekly palifermin doses at the same dose level during a 6-week Radiotherapy / chemotherapy course | Drug: Palifermin<br>* Single IV dose of palifermin at 120 μg/kg, 3 days before the start of radiotherapy plus 6 once weekly palifermin doses at the same dose level during a 6-week Radiotherapy / chemotherapy course<br>* Other names: KGF;|
| Placebo Comparator: Placebo<br>Single IV dose of placebo at 120 μg/kg, 3 days before the start of Radiotherapy, plus 6 once weekly placebo doses at the same dose during a 6-week radiotherapy / chemotherapy course. | Drug: Placebo<br>* Single IV dose of placebo at 120 μg/kg, 3 days before the start of Radiotherapy, plus 6 once weekly placebo doses at the same dose during a 6-week radiotherapy / chemotherapy course.<br>* Other names: Pbo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence percentage of severe oral mucositis (Grades 3 or 4 on the WHO oral mucositis scale) |  | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average patient-reported mouth and throat soreness score (as reported on Question 3 of the Oral Mucositis Weekly Questionnaire for patients with Head and Neck cancer [OMWQ-HN] |  | 16 weeks | 
| Time to onset of severe oral mucositis (WHO Grades 3 or 4) |  | 12 weeks | 
| Total dose of opioid analgesics used (mg of morphine equivalents) |  | 16 weeks | 
| Incidence of unplanned delays in CT for cisplatin administration on Day 22 (to include discontinuations of CT) |  | 12 weeks | 
| Incidence of xerostomia (CTCAE v3.0 Dry Mouth/Xerostomia scale Grade 2 or higher) |  | 10 years | 
| Duration of severe oral mucositis (WHO Grades 3 or 4) |  | 15 weeks | 
| Incidence of >/equal to 5 missed consecutive fractions of scheduled RT (to include discontinuations of RT) |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncology, KGF, Palifermin, Oral mucositis, Clinical Trial, Amgen, head and neck