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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy, safety and tolerability of palifermin on the incidence of oral mucositis in subjects with locally advanced head and neck cancer receiving postoperative radiotherapy.

Official Title
-----------------
A Phase 1/2 Study to Evaluate Safety, Pharmacokinetics and Preliminary Efficacy of Weekly Doses of Palifermin (Recombinant Human Keratinocyte Growth Factor, rHuKGF) for the Reduction of Oral Mucositis in Subjects With Locally Advanced Head and Neck Cancer (HNC) Receiving Postoperative Radiotherapy

Conditions
-----------------
Head and Neck Cancer

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: palifermin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: History of newly diagnosed histologically confirmed squamous cell carcinoma (AJCC Stage II, III or IVA) involving either the oral cavity, oropharynx, hypopharynx, larynx and post surgical resection (R0 or R1) Candidates for postoperative RT-only treatment and scheduled to receive RT within 12 weeks of surgery Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 Urinary protein-creatinine ratio (random sample, spot PCR) ≤ 0.2 mg/mg Exclusion Criteria: Tumors of the lips, paranasal sinuses, salivary glands, or of unknown primary tumors and R2 resection margins Metastatic disease (M1) Presence or history of any other primary malignancy, other than curatively treated in situ cervical cancer, or basal cell carcinoma of the skin without evidence of disease for > 3 years History of pancreatitis Prior radiotherapy to the site of disease Prior chemotherapy or requiring chemotherapy during treatment phase of study Prior treatment with palifermin, or other fibroblast or keratinocyte growth factors

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Approximately 17 subjects to receive palifermin. Subjects will be enrolled as follows: PK cohort will be randomized in a 3:1 ratio [palifermin: placebo] in at least 12 subjects Non-PK cohort will be randomized in a 1:1 ratio [palifermin: placebo] in up to 28 subjects. | Drug: Placebo<br>* Single IV dose of placebo, 3 days before the start of RT, then once weekly placebo doses at the same dose during a planned 6 week RT course.<br>|
| Experimental: Palifermin<br>Approximately 23 subjects to receive palifermin. Subjects will be enrolled as follows: PK cohort will be randomized in a 3:1 ratio [palifermin: placebo] in at least 12 subjects Non-PK cohort will be randomized in a 1:1 ratio [palifermin: placebo] in up to 28 subjects. | Drug: palifermin<br>* 120μg/kg, single IV, 3 days before the start of Radiotherapy (RT), then once weekly at the same dose during a planned 6-week RT course<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent proteinuria |  | 11 weeks | 
| Duration of treatment-emergent proteinuria |  | 11 weeks | 
| Incidence of chronic proteinuria |  | 11 weeks | 
| Time (days) to onset of treatment-emergent proteinuria |  | 11 weeks | 
| Maximum protein-to-creatinine ratio values during the treatment period |  | 11 weeks | 
| Pharmacokinetic profile to include Systemic clearance, volume of distribution at steady state, estimated initial concentration, area under the conc-time curve, terminal half-life and mean residual time |  | in Week 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time (days) to onset of severe Oral Mucositis WHO grade 3 or 4 |  | 11 weeks | 
| Disease status at End of Treatment visit |  | 11 weeks | 
| Incidence of serum anti-palifermin antibody formation |  | 11 weeks | 
| Incidence of second primary tumors |  | up to 10 years (Long-Term Follow-Up phase) | 
| Incidence of other malignancies |  | up to 10 years (Long-Term Follow-Up phase) | 
| Progression-free survival |  | up to 10 years (Long-Term Follow-Up phase) | 
| Overall survival |  | up to 10 years (Long-Term Follow-Up phase) | 
| Incidence of adverse events and laboratory abnormalities |  | 11 weeks | 
| Incidence (%) and duration (days) of severe Oral Mucositis WHO grade 3 or 4 |  | 11 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
KGF, Oncology, HNC, head and neck, oral mucositis, OM, proteinurea, palifermin, clinical trial