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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: Placebo; Drug: palifermin

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; 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.
Experimental: Palifermin; 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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Swedish Orphan Biovitrum
• Collaborators: Amgen
• Investigators: Study Director: MD, Biovitrum AB (publ)

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): September 1, 2008
• Study Completion (Anticipated): September 1, 2008

Study Registration Dates

• First Submitted: October 4, 2007
• First Submitted That Met QC Criteria: October 4, 2007
• First Posted (Estimate): October 8, 2007

Study Record Updates

• Last Update Posted (Estimate): March 2, 2009
• Last Update Submitted That Met QC Criteria: February 27, 2009
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Keywords: clinical trial; Oncology; palifermin; head and neck; HNC; oral mucositis; KGF; OM; proteinurea
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Head and Neck Neoplasms; Mucositis; Stomatitis
• Other Study ID Numbers: 20070201