Dysphasia MedDRA version: 14.1 Level: PT Classification code 10013950 Term: Dysphagia System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: Palifermin (Kepivance)
Product Code: V03A F08
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: palifermin
Current Sponsor code: palifermin
Concentration unit:
Sponsors
Swedish Orphan Biovitrum (Sobi) AB (publ)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Disease Related: - Patients with a histologically or cytologically proven diagnosis of NSCLC - Unresectable (locally advanced) stage IIIa or IIIb disease - Initial RT field of treatment to encompass = 30% of the esophagus - Life expectancy = 6 months - Estimated weight loss = 10% in the 3 months before study randomization - Measurable disease Demographic: - 18 years of age or older - ECOG performance status of 0-2 (see Appendix F) Screening Laboratory: - Hemoglobin (hgb) = 10 g/dL without transfusional support or growth factor use in the 4 weeks before study randomization - Absolute neutrophil count (ANC) = 1.5 x 10e9/L without growth factor use in the 2 weeks before study randomization - Platelet count = 100 x 10e9/L - Serum bilirubin = 1.5 x institutional upper limit of normal (ULN) - Serum creatinine = 2.0 mg/dL (Note: Subjects with a serum creatinine = 1.4 and = 2.0 mg/dL must demonstrate a 24-hour urinary creatinine clearance = 50 mL/min.) - Females of childbearing potential: negative serum or urine pregnancy test Ethical: - Subject must give written informed consent before participating in any study-specific procedure, randomization, or receiving investigational product. General: - Subjects with reproductive capability must agree to practice adequate contraception methods. 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 54 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 46
Exclusion criteria
Exclusion criteria: Disease Related: - Metastatic disease (M1)/stage 4 NSCLC - Pleural or pericardial effusion greater than 100 ml in volume as documented by appropriate imaging ( PET, CT scan or ultrasound). If an effusion greater than 100 ml is documented by cytology to be free from malignancy and the investigator feels the subject is capable of receiving RT/ CT for their primary disease/ NSCLC, the investigator should discuss the patient with the study physician at Amgen. Effusions smaller than 100 ml would be acceptable, unless the investigator suspects that the effusion is malignant, in which case the effusion should be evaluated by cytology. Sponsor approval must be obtained before subject is randomized. - Plan to remove the tumor surgically before completing the protocol CT/RT course - Shielding of any part of the esophagus during RT (including posterior spinal cord shielding) - Prior chemotherapy, radiotherapy, or surgery for NSCLC - Prior invasive malignancy during the past 3 years other than non-melanomatous skin cancer. Note: Subjects with prior surgically-cured malignancies [eg, stage I breast cancer or prostate cancer, in-situ carcinoma of the cervix, etc] are not excluded; however, sponsor approval must be obtained before subject is randomized. - Presence or history of dysphagia or conditions predisposing to dysphagia (eg, uncontrolled gastroesophageal reflux disease [GERD], dyspepsia, etc) - History of pancreatitis Medication/Prior Treatment: - Four weeks or less since completion of treatment using an investigational product/device in another clinical study or presence of any unresolved toxicity from previous treatment - Previous treatment on this study or with a fibroblast growth factor Laboratory: - Known to be sero-positive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) General: - Pregnant or breastfeeding women - Known sensitivity to E coli derived products - Compromised ability of the subject to give written informed consent and/or to comply with study procedures - Refusal to sign an informed consent form to participate in this study, and sign the hospital information release form, if applicable - Unwilling or unable to complete the PRO questionnaires - Psychological, social, familial, or geographical reasons that would prevent regular follow-up
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of palifermin administered at single weekly doses of 180 µg/kg in reducing the incidence of dysphagia (grade = 2) induced by concurrent chemoradiotherapy (CT/RT) followed by consolidation chemotherapy in patients with unresectable stage III non-small cell lung cancer (NSCLC).;Secondary Objective: - To evaluate the safety of palifermin administered at single weekly doses of 180 µg/kg (a total of 7 doses) - To assess the effect of palifermin on treatment-related clinical sequelae ;Primary end point(s): Incidence of dysphagia (grade = 2) measured using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale;Timepoint(s) of evaluation of this end point: All subjects will undergo dysphagia assessments using the CTCAE v3.0 dysphagia scale twice weekly during weeks 1 through 7, and twice weekly thereafter (weeks 8 through 12) until dysphagia resolves to grade = 1. Subjects still experiencing grade = 2 dysphagia at the end of week 12 will continue to have once weekly dysphagia assessments until dysphagia resolves to grade = 1 (but not beyond week 16). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary: Duration (days) of grade = 2 dysphagia - Maximum severity of dysphagia - Incidence of severe (grade = 3) dysphagia - Change in performance status and body weight (kg) - Incidence of unplanned breaks in RT (to include discontinuations of RT) - Patient-reported outcomes (PRO): - Functional Assessment of Cancer Therapy - Esophageal Cancer (FACT-E) average Swallowing Index score during the acute dysphagia evaluation phase (baseline through week 12) - Related Clinical Sequelae - Incidence and cumulative dose of opioid analgesics use (morphine equivalents) - Incidence and duration (days) of hospitalization - Incidence of percutaneous endoscopic gastrostomy (PEG)/nasogastric (NG) tube, total parenteral nutrition (TPN), and IV hydration use - Incidence of infections Short term safety: - Incidence of adverse events (AEs) and laboratory abnormalities using the CTCAE v3.0 toxicity criteria - Incidence of serum anti-palifermin antibody formation - Tumor response at week Long term safety: - Incidence of chronic dysphagia defined as unresolved dysphagia (grade = 2) at month 6 - Incidence of pneumonitis measured using the Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) Late Radiation Morbidity Scoring Schema - Incidence of second primary tumors - Incidence of other malignancies - Progression-free survival (PFS) - Overall survival (OS);Timepoint(s) of evaluation of this end point: All subjects will undergo dysphagia assessments using the CTCAE v3.0 dysphagia scale twice weekly during weeks 1 through 7, and twice weekly thereafter (weeks 8 through 12) until dysphagia resolves to grade = 1. Subjects still experiencing grade = 2 dysphagia at the end of week 12 will continue to have once weekly dysphagia assessments until dysphagia resolves to grade = 1 (but not beyond week 16). Long-term follow-up will end after 5 years from the last subject randomized. | — |
Countries
France, Germany, Poland, Spain, United States
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed