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
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Head and Neck Cancer
- Sponsor
- Swedish Orphan Biovitrum
- Primary Endpoint
- Incidence of treatment-emergent proteinuria
- Status
- Withdrawn
- Last Updated
- 17 years ago
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.
Investigators
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
Arms & Interventions
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.
Intervention: Placebo
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.
Intervention: palifermin
Outcomes
Primary Outcomes
Incidence of treatment-emergent proteinuria
Time Frame: 11 weeks
Duration of treatment-emergent proteinuria
Time Frame: 11 weeks
Incidence of chronic proteinuria
Time Frame: 11 weeks
Time (days) to onset of treatment-emergent proteinuria
Time Frame: 11 weeks
Maximum protein-to-creatinine ratio values during the treatment period
Time Frame: 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
Time Frame: in Week 1
Secondary Outcomes
- 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)