Oral Mucositis MedDRA version: 18.0 Level: LLT Classification code 10028130 Term: Mucositis oral System Organ Class: 100000004856
Conditions
Interventions
Product Name: Palifermin (kepivance)
Product Code: V03A F08
Pharmaceutical Form: Powder for solution for injection
Pharmaceutical form of the placebo: Powder for solution for injection
Route of admini
Sponsors
Swedish Orphan Biovitrum AB (publ.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed informed consent • =18 years of age • History of newly diagnosed histologically confirmed squamous cell carcinoma (AJCC Stage II, III, IVA, or IVB) involving either the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx, post surgical resection (R0, R1) and candidates for adjuvant RT/CT • High-risk subject defined by presence of at least one of the following: R1 resection margins; T3 or T4 tumor stage; 3 or more positive lymph node metastases; 3.5 x 109/L or absolute neutrophil count (ANC) > 1.5 x 109/L - Platelet count = 100 x 109/L - Serum bilirubin = 1.5 x institutional upper limits of normal (ULN) - Serum creatinine = 2.0 mg/dL; Subjects with a serum creatinine = 1.4 mg/dL and = 2.0 mg/dL need to demonstrate a 24-hr urinary creatinine clearance = 50 mL/min - Females of childbearing potential: negative serum or urine pregnancy test Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: • Tumors of the lips, paranasal sinuses, salivary glands, or of unknown primary tumors • Metastatic disease (M1) / Stage IV C • Presence or history of any other primary malignancy • History of pancreatitis • Prior radiotherapy to the site of disease • Prior chemotherapy • Other investigational procedures • Thirty days or less since receiving an investigational product or device in another clinical trial. Current enrollment in another clinical trial is not permitted unless the sole purpose of the trial is for long-term follow-up/survival data. • Pregnant or breast-feeding women permitted unless the sole purpose of the trial is for long-term follow-up/survival data. • Refusal to use adequate contraceptive devices during treatment phase • Known sensitivity to any of the products administered during dosing, including E coli-derived products • Known to be sero-positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) • Previous treatment on this study or with other keratinocyte growth factors • Compromised ability of the subject to give written informed consent and/or to comply with study procedures • Refusal to give written informed consent to participate in this study and to sign the hospital information release form • Unwilling or unable to complete the patient-reported outcome questionnaires • Psychological, social, familial, or geographical reasons that would prevent regular follow-up.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the pharmacokinetic profile and biological activity on buccal mucosae of palifermin administered at the dose of 120 µg/kg IV in a cohort of at least 16 (3 palifermin : 1 placebo) locally advanced HNC subjects receiving RT with concurrent CT as adjuvant treatment for their disease (post-operative setting). To evaluate the safety and tolerability of palifermin when administered at the dose of 120 µg/kg weekly for up to 8 consecutive weeks to patients with locally advanced HNC receiving RT with concurrent CT as adjuvant treatment for their disease (post-operative setting).;Secondary Objective: To assess the preliminary efficacy of 120 µg/kg palifermin in reducing the incidence and duration of severe oral mucositis (OM) (Adapted RTOG/EORTC grade =3) To assess the preliminary efficacy of palifermin on the clinical sequelae of OM and Patient-reported mouth and throat soreness (MTS) To evaluate long-term effects of palifermin on disease outcome and survival.;Primary end point(s): Pharmacokinetic endpoints: PK endpoints will include, but are not limited to: • systemic clearance (CL) • volume of distribution at steady state (Vss) • estimated initial concentration (C0) • area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC(0-t)) and to infinity (AUC(0-8)) • terminal half-life (t1/2,z) • mean residence time (MRT) Pharmacodynamics Endpoints The primary PD endpoint will be cell proliferation assayed by staining for cell cycle proliferation marker Ki67. Safety and Efficacy Endpoints: Proportion of subjects with protocol-specific limiting toxicity • Incidence of adverse events and laboratory abnormalities using the CTCAE v.3.0 toxicity scales • Incidence (%) and duration (days) of severe oral mucositis (Adapted RTOG/EORTC) grade =3 • Time (days) to onset of severe oral mucositis (Adapted RTOG/EORTC grade =3) • Incidence (%) and duration (days) of oral mucositis (Adapted RTOG/EORTC grade =2) • Ti | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Exploratory endpoints Evaluation of potential biomarkers with respect to chemo/radiotherapy-induced oral mucositis and treatment regimen Evaluation of genetic variation as related to presence of mucositis and patient response to treatment;Timepoint(s) of evaluation of this end point: Evaluations of oral mucosal surfaces (mucositis assessments) occur daily (weekdays) throughout CT/RT, then 2 times weekly thereafter until mucositis has resolved to Grade = 2, once mucositis has resolved to Grade = 2 subjects will return to the clinic for mucositis assessments once a week until mucositis has resolved to grade = 1. If OM does not resolve to Grade = 1 by week 15, subjects should continue to have a once weekly assessment until resolution to Grade = 1 but not beyond week 24 / month 6. | — |
Countries
Germany
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed