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

Sponsor

Swedish Orphan Biovitrum (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT00540332

Collaborator

Amgen (Industry)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: Placebo Drug: palifermin	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Supportive Care

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

Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Sep 1, 2008

Anticipated Study Completion Date :

Sep 1, 2008

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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